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Protective Effects of Antioxidants in Huntington’s Disease: an Extensive Review

  • Musthafa Mohamed Essa
  • Marzieh Moghadas
  • Taher Ba-Omar
  • M. Walid Qoronfleh
  • Gilles J. Guillemin
  • Thamilarasan Manivasagam
  • Arokiasamy Justin-Thenmozhi
  • Bipul Ray
  • Abid Bhat
  • Saravana Babu Chidambaram
  • Amanda J Fernandes
  • Byoung-Joon Song
  • Mohammed Akbar
Review Article
  • 33 Downloads

Abstract

Huntington’s disease (HD) is a hereditary neurodegenerative disease of the central nervous system (CNS). Onset of HD occurs between the ages of 30 and 50 years, although few cases are reported among children and elderly. HD appears to be less common in some populations such as those of Japanese, Chinese, and African descent. Clinical features of HD include motor dysfunction (involuntary movements of the face and body, abnormalities in gait, posture and balance), cognitive impairment (obsessive-compulsive disorder), and psychiatric disorders (dementia). Mutation in either of the two copies of a gene called huntingtin (HTT), which codes genetic information for a protein called “huntingtin (Htt)”, precipitates the disease in an individual. Expansion of cytosine–adenine–guanine (CAG) triplet repeats in the HTT gene results in an abnormal Htt protein. Intracellular neuronal accumulation of the mutated Htt protein (mHtt) causes distinctive erratic movements associated with HD. Further, excessive accumulation of the HTT gene repeats causes abnormal production of reactive oxygen species (ROS) and the ensuing mitochondrial (MT) oxidative stress in neurons. Since there is neither a cure nor a promising strategy to delay onset or progression of HD currently available, therapeutics are mainly focusing only on symptomatic management. Several studies have shown that MT dysfunction-mediated oxidative stress is a key factor for the neurodegeneration observed in HD. Supplementation of antioxidants and nutraceuticals has been widely studied in the management of oxidative damage, an associated complication in HD. Therefore, various antioxidants are used as therapeutics for managing and/or treating HD. The present review aimed at delving into the abnormal cellular changes and energy kinetics of the neurons expressing the mHtt gene and the therapeutic roles of antioxidants in HD.

Keywords

Huntington’s disease Oxidative stress Neurodegeneration Free radicals Reactive oxygen/nitrogen species Antioxidants 

Abbreviations

HD

Huntington’s disease

HTT

Huntington gene

Htt

Huntington protein

ROS

Reactive oxygen species

MT

Mitochondrial

polyQ

Polyglutamine

MSNs

Medium spiny neurons

mHtt

Mutant huntingtin

NMDA

N-methyl-d-aspartate

Notes

Acknowledgements

The authors gratefully acknowledge their respective institutions and the support provided by SQU (IG/AGR/FOOD/17/02) in the form of an internal grant. The technical and language editing support was provided by The Editing Refinery, MD, USA, and is highly acknowledged.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. Abd-El-Fattah AA, El-Sawalhi MM, Rashed ER, El-Ghazaly MA (2010) Possible role of vitamin E, coenzyme Q10 and rutin in protection against cerebral ischemia/reperfusion injury in irradiated rats. Int J Radiat Bio 86:1070–1078.  https://doi.org/10.3109/09553002.2010.501844 CrossRefGoogle Scholar
  2. Achour M, Le Gras S, Keime C, Parmentier F, Lejeune FX, Boutillier AL, Néri C, Davidson I, Merienne K (2015) Neuronal identity genes regulated by super-enhancers are preferentially down-regulated in the striatum of Huntington’s disease mice. Hum Mol Genet 24:3481–3496.  https://doi.org/10.1093/hmg/ddv099 CrossRefPubMedGoogle Scholar
  3. ACMG/ASHG statement (1998) Laboratory guidelines for Huntington disease genetic testing. The American College of Medical Genetics/American Society of Human Genetics Huntington Disease Genetic Testing Working Group. Am J Hum Genet 62(5):1243–1247CrossRefGoogle Scholar
  4. Acuña AI, Esparza M, Kramm C, Beltrán FA, Parra AV, Cepeda C, Toro CA, Vidal RL, Hetz C, Concha II, Brauchi S, Levine MS, Castro MA (2013) A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington’s disease in mice. Nat Commun 4:2917.  https://doi.org/10.1038/ncomms3917
  5. Adibhatla RM, Hatcher JF (2010) Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 12:125–169.  https://doi.org/10.1089/ars.2009.2668 CrossRefPubMedGoogle Scholar
  6. Albin RL, Reiner A, Anderson KD, Dure LS, Handelin B, Balfour R, Whetsell WO, Penney JB, Young AB (1992) Preferential loss of striato-external pallidal projection neurons in presymptomatic Huntington’s disease. Ann Neurol 31:425–430.  https://doi.org/10.1002/ana.410310412 CrossRefPubMedGoogle Scholar
  7. Aleksandrov PN, Speranskaia TV, Bobkov IG, Zagorevskiĭ VA, Zykov DA (1986) Effect of rutin and esculamine on models of aseptic inflammation. Farmakol Toksikol 49:84–86PubMedGoogle Scholar
  8. Alexi T, Hughes PE, Faull RL, Williams CE (1998) 3-Nitropropionic acid's lethal triplet: cooperative pathways of neurodegeneration. Neuroreport 9(11):57–64CrossRefGoogle Scholar
  9. André VM, Cepeda C, Levine MS (2010) Dopamine and glutamate in Huntington’s disease: a balancing act. CNS Neurosci Ther 16:163–178.  https://doi.org/10.1111/j.1755-5949.2010.00134.x CrossRefPubMedPubMedCentralGoogle Scholar
  10. Andreassen OA, Dedeoglu A, Ferrante RJ, Jenkins BG, Ferrante KL, Thomas M, Friedlich A, Browne SE, Schilling G, Borchelt DR, Hersch SM, Ross CA, Beal MF (2001) Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington’s disease. Neurobiol Dis 8:479–491PubMedCrossRefGoogle Scholar
  11. Andrews TC, Brooks DJ (1998) Advances in the understanding of early Huntington’s disease using the functional imaging techniques of PET and SPET. Mol Med Today 4:532–539PubMedCrossRefGoogle Scholar
  12. Antunes Wilhelm E, Ricardo Jesse C, Folharini Bortolatto C, Wayne Nogueira C (2013) Correlations between behavioural and oxidative parameters in a rat quinolinic acid model of Huntington’s disease: protective effect of melatonin. Eur J Pharmacol 701:65–72.  https://doi.org/10.1016/j.ejphar.2013.01.007 CrossRefPubMedGoogle Scholar
  13. Arakawa M, Ito Y (2007) N-acetylcysteine and neurodegenerative diseases: basic and clinical pharmacology. Cerebellum 6:308–314.  https://doi.org/10.1080/14734220601142878 CrossRefPubMedGoogle Scholar
  14. Ariano MA, Aronin N, Difiglia M, Tagle DA, Sibley DR, Leavitt BR, Hayden MR, Levine MS (2002) Striatal neurochemical changes in transgenic models of Huntington’s disease. J Neurosci Res 68:716–729.  https://doi.org/10.1002/jnr.10272 CrossRefPubMedGoogle Scholar
  15. Ashrafi G, Schwarz TL (2015) PINK1- and PARK2-mediated local mitophagy in distal neuronal axons. Autophagy 11:187–189.  https://doi.org/10.1080/15548627.2014.996021 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Aufschnaiter A, Kohler V, Büttner S (2017) Taking out the garbage: cathepsin D and calcineurin in neurodegeneration. Neural Regen Res 12:1776–1779.  https://doi.org/10.4103/1673-5374.219031 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Aziz NA, Pijl H, Frölich M, Schröder-van der Elst JP, van der Bent C, Roelfsema F, Roos RAC (2009) Delayed onset of the diurnal melatonin rise in patients with Huntington’s disease. J Neurol 256:1961–1965.  https://doi.org/10.1007/s00415-009-5196-1 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Baig SS, Strong M, Quarrell OW (2016) The global prevalence of Huntington’s disease: a systematic review and discussion. Neurodegener Dis Manag 6:331–343.  https://doi.org/10.2217/nmt-2016-0008 CrossRefPubMedGoogle Scholar
  19. Bates GP, Dorsey R, Gusella JF, Hayden MR, Kay C, Leavitt BR, Nance M, Ross CA, Scahill RI, Wetzel R, Wild EJ, Tabrizi SJ (2015) Huntington disease. Nat Rev Dis Primers 1:15005.  https://doi.org/10.1038/nrdp.2015.5 CrossRefPubMedGoogle Scholar
  20. Beal MF (1998) Mitochondrial dysfunction in neurodegenerative diseases. Biochim Biophys Acta 1366:211–223PubMedCrossRefGoogle Scholar
  21. Beal MF (2005) Mitochondria take center stage in aging and neurodegeneration. Ann Neurol 58:495–505.  https://doi.org/10.1002/ana.20624 CrossRefPubMedGoogle Scholar
  22. Beal MF (2011) Neuroprotective effects of creatine. Amino Acids 40:1305–1313.  https://doi.org/10.1007/s00726-011-0851-0 CrossRefPubMedGoogle Scholar
  23. Beal MF, Brouillet E, Jenkins BG, Ferrante RJ, Kowall NW, Miller JM, Storey E, Srivastava R, Rosen BR, Hyman BT (1993) Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J Neurosci 13:4181–4192PubMedCrossRefGoogle Scholar
  24. Behrens PF, Franz P, Woodman B, Lindenberg KS, Landwehrmeyer GB (2002) Impaired glutamate transport and glutamate–glutamine cycling: downstream effects of the Huntington mutation. Brain 125:1908–1922.  https://doi.org/10.1093/brain/awf180 CrossRefPubMedGoogle Scholar
  25. Bender A, Auer DP, Merl T, Reilmann R, Saemann P, Yassouridis A, Bender J, Weindl A, Dose M, Gasser T, Klopstock T (2005) Creatine supplementation lowers brain glutamate levels in Huntington’s disease. J Neurol 252:36–41.  https://doi.org/10.1007/s00415-005-0595-4 CrossRefPubMedGoogle Scholar
  26. Berk M, Malhi GS, Gray LJ, Dean OM (2013) The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci 34:167–177.  https://doi.org/10.1016/j.tips.2013.01.001 CrossRefPubMedGoogle Scholar
  27. Berr C, Portet F, Carriere I, Akbaraly TN, Feart C, Gourlet V, Combe N, Barberger-Gateau P, Ritchie K (2009) Olive oil and cognition: results from the three-city study. Dement Geriatr Cogn Disord 28:357–364.  https://doi.org/10.1159/000253483 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Bibb JA, Yan Z, Svenningsson P, Snyder GL, Pieribone VA, Horiuchi A, Nairn AC, Messer A, Greengard P (2000) Severe deficiencies in dopamine signaling in presymptomatic Huntington’s disease mice. Proc Natl Acad Sci U S A 97:6809–6814.  https://doi.org/10.1073/pnas.120166397 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Bizat N, Hermel JM, Boyer F, Jacquard C, Créminon C, Ouary S, Escartin C, Hantraye P, Kajewski S, Brouillet E (2003) Calpain is a major cell death effector in selective striatal degeneration induced in vivo by 3-nitropropionate: implications for Huntington’s disease. J Neurosci 23:5020–5030Google Scholar
  30. Bonilla E (2000) Huntington disease. A review. Invest Clin 41:117–141PubMedGoogle Scholar
  31. Borlongan CV, Koutouzis TK, Freeman TB, Cahill DW, Sanberg PR (1995) Behavioral pathology induced by repeated systemic injections of 3-nitropropionic acid mimics the motoric symptoms of Huntington’s disease. Brain Res 697:254–257PubMedCrossRefGoogle Scholar
  32. Bortolatto CF, Jesse CR, Wilhelm EA, Chagas PM, Nogueira CW (2013) Organoselenium bis selenide attenuates 3-nitropropionic acid-induced neurotoxicity in rats. Neurotox Res 23:214–224.  https://doi.org/10.1007/s12640-012-9336-5
  33. Bowles KR, Brooks SP, Dunnett SB, Jones L (2012) Gene expression and behaviour in mouse models of HD. Brain Res Bull 88:276–284.  https://doi.org/10.1016/j.brainresbull.2011.07.021 CrossRefPubMedGoogle Scholar
  34. Braak H, Braak E (1992) Allocortical involvement in Huntington’s disease. Neuropathol Appl Neurobiol 18:539–547.  https://doi.org/10.1111/j.1365-2990.1992.tb00824.x CrossRefPubMedGoogle Scholar
  35. Brennan WA, Bird ED, Aprille JR (1985) Regional mitochondrial respiratory activity in Huntington’s disease brain. J Neurochem 44:1948–1950PubMedCrossRefGoogle Scholar
  36. Brignull HR, Morley JF, Garcia SM, Morimoto RI (2006) Modeling polyglutamine pathogenesis in C. elegans. Meth Enzymol 412:256–282.  https://doi.org/10.1016/S0076-6879(06)12016-9 CrossRefPubMedGoogle Scholar
  37. Brocardo SP, Gil-Mohapel MJ (2012) Therapeutic strategies for Huntington’s disease: from the bench to the clinic. Current Psychopharmacology 1:137–154 Google Scholar
  38. Brocardo PS, McGinnis E, Christie BR, Gil-Mohapel J (2016) Time-course analysis of protein and lipid oxidation in the brains of Yac128 Huntington’s disease transgenic mice. Rejuvenation Res 19(2):140–148.  https://doi.org/10.1089/rej.2015.1736 CrossRefPubMedGoogle Scholar
  39. Brouillet E, Jenkins BG, Hyman BT, Ferrante RJ, Kowall NW, Srivastava R, Roy DS, Rosen BR, Beal MF (1993) Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid. J Neurochem 60:356–359PubMedCrossRefGoogle Scholar
  40. Brouillet E, Guyot MC, Mittoux V, Altairac S, Condé F, Palfi S, Hantraye P (1998) Partial inhibition of brain succinate dehydrogenase by 3-nitropropionic acid is sufficient to initiate striatal degeneration in rat. J Neurochem 70:794–805PubMedCrossRefGoogle Scholar
  41. Browne SE, Beal MF (2004) The energetics of Huntington’s disease. Neurochem Res 29:531–546PubMedCrossRefGoogle Scholar
  42. Browne SE, Beal MF (2006) Oxidative damage in Huntington’s disease pathogenesis. Antioxid Redox Signal 8:2061–2073.  https://doi.org/10.1089/ars.2006.8.2061 CrossRefPubMedGoogle Scholar
  43. Browne SE, Ferrante RJ, Beal MF (1999) Oxidative stress in Huntington’s disease. Brain Pathol 9:147–163PubMedCrossRefGoogle Scholar
  44. Butterworth NJ, Williams L, Bullock JY, Love DR, Faull RL, Dragunow M (1998) Trinucleotide (CAG) repeat length is positively correlated with the degree of DNA fragmentation in Huntington’s disease striatum. Neuroscience 87:49–53PubMedCrossRefGoogle Scholar
  45. Calkins MJ, Jakel RJ, Johnson DA, Chan K, Kan YW, Johnson JA (2005) Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription. Proc Natl Acad Sci U S A 102:244–249.  https://doi.org/10.1073/pnas.0408487101 CrossRefPubMedGoogle Scholar
  46. Carmo C, Naia L, Lopes C, Rego AC (2018) Mitochondrial dysfunction in Huntington’s disease. Adv Exp Med Biol 1049:59–83.  https://doi.org/10.1007/978-3-319-71779-1_3 CrossRefPubMedGoogle Scholar
  47. Castro M, Caprile T, Astuya A, Millán C, Reinicke K, Vera JC, Vásquez O, Aguayo LG, Nualart F (2001) High-affinity sodium-vitamin C co-transporters (SVCT) expression in embryonic mouse neurons. J Neurochem 78:815–823PubMedCrossRefGoogle Scholar
  48. Castro MA, Pozo M, Cortés C, García MLA, Concha II, Nualart F (2007) Intracellular ascorbic acid inhibits transport of glucose by neurons, but not by astrocytes. J Neurochem 102:773–782.  https://doi.org/10.1111/j.1471-4159.2007.04631.x CrossRefPubMedGoogle Scholar
  49. Castro MA, Angulo C, Brauchi S, Nualart F, Concha II (2008) Ascorbic acid participates in a general mechanism for concerted glucose transport inhibition and lactate transport stimulation. Pflugers Arch 457:519–528.  https://doi.org/10.1007/s00424-008-0526-1 CrossRefPubMedGoogle Scholar
  50. Castro MA, Beltrán FA, Brauchi S, Concha II (2009) A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid. J Neurochem 110:423–440.  https://doi.org/10.1111/j.1471-4159.2009.06151.x CrossRefPubMedGoogle Scholar
  51. Cattaneo E, Rigamonti D, Goffredo D, Zuccato C, Squitieri F, Sipione S (2001) Loss of normal huntingtin function: new developments in Huntington’s disease research. Trends Neurosci 24:182–188PubMedCrossRefGoogle Scholar
  52. Caviston JP, Ross JL, Antony SM, Tokito M, Holzbaur ELF (2007) Huntingtin facilitates dynein/dynactin-mediated vesicle transport. Proc Natl Acad Sci U S A 104:10045–10050.  https://doi.org/10.1073/pnas.0610628104 CrossRefPubMedPubMedCentralGoogle Scholar
  53. Cepeda C, Hurst RS, Calvert CR, Hernández-Echeagaray E, Nguyen OK, Jocoy E, Christian LJ, Ariano MA, Levine MS (2003) Transient and progressive electrophysiological alterations in the corticostriatal pathway in a mouse model of Huntington’s disease. J Neurosci 23:961–969PubMedCrossRefGoogle Scholar
  54. Cepeda C, Murphy KPS, Parent M, Levine MS (2014) The role of dopamine in Huntington’s disease. Prog Brain Res 211:235–254.  https://doi.org/10.1016/B978-0-444-63425-2.00010-6 CrossRefPubMedPubMedCentralGoogle Scholar
  55. Cha JH, Kosinski CM, Kerner JA, Alsdorf SA, Mangiarini L, Davies SW, Penney JB, Bates GP, Young AB (1998a) Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci U S A 95:6480–6485PubMedPubMedCentralCrossRefGoogle Scholar
  56. Cha JH, Kosinski CM, Kerner JA, Alsdorf SA, Mangiarini L, Davies SW, Penney JB, Bates GP, Young AB (1998b) Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci U S A 95:6480–6485PubMedPubMedCentralCrossRefGoogle Scholar
  57. Cha JH, Frey AS, Alsdorf SA, Kerner JA, Kosinski CM, Mangiarini L, Penney JB, Davies SW, Bates GP, Young AB (1999) Altered neurotransmitter receptor expression in transgenic mouse models of Huntington’s disease. Philos Trans R Soc Lond Ser B Biol Sci 354:981–989CrossRefGoogle Scholar
  58. Chang CR, Blackstone C (2010) Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1. Ann N Y Acad Sci 1201:34–39.  https://doi.org/10.1111/j.1749-6632.2010.05629.x CrossRefPubMedPubMedCentralGoogle Scholar
  59. Chang DTW, Rintoul GL, Pandipati S, Reynolds IJ (2006) Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons. Neurobiol Dis 22:388–400.  https://doi.org/10.1016/j.nbd.2005.12.007 CrossRefPubMedGoogle Scholar
  60. Chen S, Gong J, Liu F, Mohammed U (2000) Naturally occurring polyphenolic antioxidants modulate IgE-mediated mast cell activation. Immunology 100:471–480PubMedPubMedCentralCrossRefGoogle Scholar
  61. Chen CM, Wu YR, Cheng ML, Liu JL, Lee YM, Lee PW, Soong BW, Chiu DTY (2007) Increased oxidative damage and mitochondrial abnormalities in the peripheral blood of Huntington’s disease patients. Biochem Biophys Res Commun 359:335–340.  https://doi.org/10.1016/j.bbrc.2007.05.093 CrossRefPubMedGoogle Scholar
  62. Cho IH (2012) Effects of Panax ginseng in neurodegenerative diseases. J Ginseng Res 36:342–353.  https://doi.org/10.5142/jgr.2012.36.4.342 CrossRefPubMedPubMedCentralGoogle Scholar
  63. Choo YS, Johnson GVW, MacDonald M, Detloff PJ, Lesort M (2004) Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. Hum Mol Genet 13:1407–1420.  https://doi.org/10.1093/hmg/ddh162 CrossRefPubMedGoogle Scholar
  64. Colle D, Santos DB, Moreira ELG, Hartwig JM, dos Santos AA, Zimmermann LT, Hort MA, Farina M (2013) Probucol increases striatal glutathione peroxidase activity and protects against 3-nitropropionic acid-induced pro-oxidative damage in rats. PLoS One 8:67658.  https://doi.org/10.1371/journal.pone.0067658 CrossRefGoogle Scholar
  65. Consortium HD, iPSC (2017) Developmental alterations in Huntington’s disease neural cells and pharmacological rescue in cells and mice. Nat Neurosci 20(5):648–660.  https://doi.org/10.1038/nn.4532 CrossRefGoogle Scholar
  66. Costa V, Giacomello M, Hudec R, Lopreiato R, Ermak G, Lim D, Malorni W, Davies KJA, Carafoli E, Scorrano L (2010) Mitochondrial fission and cristae disruption increase the response of cell models of Huntington’s disease to apoptotic stimuli. EMBO Mol Med 2:490–503.  https://doi.org/10.1002/emmm.201000102 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Costall B, Kelly ME, Naylor RJ (1984) The antidyskinetic action of dihomo-γ-linolenic acid in the rodent. Br J Pharmacol 83:733–740.  https://doi.org/10.1111/j.1476-5381.1984.tb16227.x CrossRefPubMedPubMedCentralGoogle Scholar
  68. Covarrubias-Pinto A, Moll P, Solís-Maldonado M, Acuña AI, Riveros A, Miró MP, Papic E, Beltrán FA, Cepeda C, Concha II, Brauchi S, Castro MA (2015) Beyond the redox imbalance: oxidative stress contributes to an impaired GLUT3 modulation in Huntington’s disease. Free Radic Biol Med 89:1085–1096.  https://doi.org/10.1016/j.freeradbiomed.2015.09.024
  69. Covas MI, Nyyssönen K, Poulsen HE, Kaikkonen J, HJF Z, Kiesewetter H, Gaddi A, de la Torre R, Mursu J, Bäumler H, Nascetti S, Salonen JT, Fitó M, Virtanen J, Marrugat J, EUROLIVE Study Group (2006) The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med 145:333–341PubMedCrossRefGoogle Scholar
  70. Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262:689–695PubMedCrossRefGoogle Scholar
  71. Coyle JT, Schwarcz R (1976) Lesion of striatal neurones with kainic acid provides a model for Huntington's chorea. Nature 263(5574):244–246PubMedCrossRefGoogle Scholar
  72. Cruz T, Gálvez J, Ocete MA, Crespo ME, Sánchez de Medina LHF, Zarzuelo A (1998) Oral administration of rutoside can ameliorate inflammatory bowel disease in rats. Life Sci 62:687–695PubMedCrossRefGoogle Scholar
  73. Damiano M, Galvan L, Déglon N, Brouillet E (2010) Mitochondria in Huntington’s disease. Biochim Biophys Acta 1802:52–61.  https://doi.org/10.1016/j.bbadis.2009.07.012
  74. Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90:537–548PubMedCrossRefGoogle Scholar
  75. Dean O, Giorlando F, Berk M (2011) N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci 36:78–86.  https://doi.org/10.1503/jpn.100057 CrossRefPubMedPubMedCentralGoogle Scholar
  76. Delanty N, Dichter MA (2000) Antioxidant therapy in neurologic disease. Arch Neurol 57:1265–1270.  https://doi.org/10.1001/archneur.57.9.1265 CrossRefPubMedGoogle Scholar
  77. Díaz RJ, Yago MD, Martínez-Victoria E, Naranjo JA, Martínez MA, Mañas M (2003) Comparison of the effects of dietary sunflower oil and virgin olive oil on rat exocrine pancreatic secretion in vivo. Lipids 38:1119–1126PubMedCrossRefGoogle Scholar
  78. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277:1990–1993PubMedCrossRefGoogle Scholar
  79. DiFiglia T, Ben-Zvi A, Ho KH, Brignull HR, Morimoto RI (2006) Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 311:1471–1474.  https://doi.org/10.1126/science.1124514 CrossRefGoogle Scholar
  80. Dinkova-Kostova AT, Liby KT, Stephenson KK, Holtzclaw WD, Gao X, Suh N, Williams C, Risingsong R, Honda T, Gribble GW, Sporn MB, Talalay P (2005) Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress. Proc Natl Acad Sci U S A 102:4584–4589.  https://doi.org/10.1073/pnas.0500815102 CrossRefPubMedPubMedCentralGoogle Scholar
  81. DiProspero NA, Chen EY, Charles V, Plomann M, Kordower JH, Tagle DA (2004) Early changes in Huntington’s disease patient brains involve alterations in cytoskeletal and synaptic elements. J Neurocytol 33:517–533.  https://doi.org/10.1007/s11068-004-0514-8 CrossRefPubMedGoogle Scholar
  82. Dowie MJ, Bradshaw HB, Howard ML, Nicholson LFB, Faull RLM, Hannan AJ, Glass M (2009) Altered CB1 receptor and endocannabinoid levels precede motor symptom onset in a transgenic mouse model of Huntington’s disease. Neuroscience 163:456–465.  https://doi.org/10.1016/j.neuroscience.2009.06.014 CrossRefPubMedGoogle Scholar
  83. Feigin A (1998) Advances in Huntington’s disease: implications for experimental therapeutics. Curr Opin Neurol 11:357–362PubMedCrossRefGoogle Scholar
  84. Feigin A, Kieburtz K, Como P, Hickey C, Claude K, Abwender D, Zimmerman C, Steinberg K, Shoulson I (1996) Assessment of coenzyme Q10 tolerability in Huntington’s disease. Mov Disord 11:321–323.  https://doi.org/10.1002/mds.870110317 CrossRefPubMedGoogle Scholar
  85. Fernández SP, Wasowski C, Loscalzo LM, Granger RE, Johnston GAR, Paladini AC, Marder M (2006) Central nervous system depressant action of flavonoid glycosides. Eur J Pharmacol 539:168–176.  https://doi.org/10.1016/j.ejphar.2006.04.004 CrossRefPubMedGoogle Scholar
  86. Ferrante RJ (2009) Mouse models of Huntington’s disease and methodological considerations for therapeutic trials. Biochim Biophys Acta 1792:506–520.  https://doi.org/10.1016/j.bbadis.2009.04.001 CrossRefPubMedPubMedCentralGoogle Scholar
  87. Ferrante RJ, Kowall NW, Beal MF, Richardson EP, Bird ED, Martin JB (1985) Selective sparing of a class of striatal neurons in Huntington’s disease. Science 230:561–563PubMedCrossRefGoogle Scholar
  88. Ferrante RJ, Andreassen OA, Jenkins BG, Dedeoglu A, Kuemmerle S, Kubilus JK, Kaddurah-Daouk R, Hersch SM, Beal MF (2000) Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J Neurosci 20(12):4389–4397PubMedCrossRefGoogle Scholar
  89. Ferrante RJ, Andreassen OA, Dedeoglu A, Ferrante KL, Jenkins BG, Hersch SM, Beal MF (2002) Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington’s disease. J Neurosci 22:1592–1599PubMedCrossRefGoogle Scholar
  90. Fink AL (1998) Protein aggregation: folding aggregates, inclusion bodies and amyloid. Fold Des 3:9–23.  https://doi.org/10.1016/S1359-0278(98)00002-9 CrossRefGoogle Scholar
  91. Fitó M, de la Torre R, Farré-Albaladejo M, Khymenetz O, Marrugat J, Covas MI (2007) Bioavailability and antioxidant effects of olive oil phenolic compounds in humans: a review. Ann Ist Super Sanita 43:375–381PubMedGoogle Scholar
  92. Fontaine MA, Geddes JW, Banks A, Butterfield DA (2000) Effect of exogenous and endogenous antioxidants on 3-nitropionic acid-induced in vivo oxidative stress and striatal lesions: insights into Huntington’s disease. J Neurochem 75:1709–1715PubMedCrossRefGoogle Scholar
  93. Gao B, Doan A, Hybertson BM (2014) The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders. Clin Pharmacol 6:19–34.  https://doi.org/10.2147/CPAA.S35078 CrossRefPubMedPubMedCentralGoogle Scholar
  94. Gauthier LR, Charrin BC, Borrell-Pagès M, Dompierre JP, Rangone H, Cordelières FP, De Mey J, MacDonald ME, Lessmann V, Humbert S, Saudou F (2004) Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 118:127–138.  https://doi.org/10.1016/j.cell.2004.06.018 CrossRefPubMedGoogle Scholar
  95. Gervais FG, Singaraja R, Xanthoudakis S, Gutekunst CA, Leavitt BR, Metzler M, Hackam AS, Tam J, Vaillancourt JP, Houtzager V, Rasper DM, Roy S, Hayden MR, Nicholson DW (2002) Recruitment and activation of caspase-8 by the huntingtin-interacting protein Hip-1 and a novel partner Hippi. Nat Cell Biol 4:95–105.  https://doi.org/10.1038/ncb735 CrossRefPubMedGoogle Scholar
  96. Geuze E, Vermetten E, Bremner JD (2005) MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Mol Psychiatry 10:160–184.  https://doi.org/10.1038/sj.mp.4001579 CrossRefPubMedGoogle Scholar
  97. Ghasemzadeh B, Cammack J, Adams RN, Ghasemzedah B (1991) Dynamic changes in extracellular fluid ascorbic acid monitored by in vivo electrochemistry. Brain Res 547:162–166PubMedGoogle Scholar
  98. Gil JM, Rego AC (2008) Mechanisms of neurodegeneration in Huntington’s disease. Eur J Neurosci 27:2803–2820.  https://doi.org/10.1111/j.1460-9568.2008.06310.x CrossRefPubMedGoogle Scholar
  99. Gil JM, Leist M, Popovic N, Brundin P, Petersén Å (2004) Asialoerythropoetin is not effective in the R6/2 line of Huntington’s disease mice. BMC Neurosci 5:17.  https://doi.org/10.1186/1471-2202-5-17 CrossRefPubMedPubMedCentralGoogle Scholar
  100. Gil-Mohapel J, Brocardo PS, Christie BR (2014) The role of oxidative stress in Huntington’s disease: are antioxidants good therapeutic candidates? Curr Drug Targets 15:454–468PubMedCrossRefGoogle Scholar
  101. Giralt A, Saavedra A, Alberch J, Pérez-Navarro E (2012) Cognitive dysfunction in Huntington’s disease: humans, mouse models and molecular mechanisms. J Huntingtons Dis 1(2):155–173.  https://doi.org/10.3233/JHD-120023s CrossRefPubMedGoogle Scholar
  102. González-Correa JA, Navas MD, Lopez-Villodres JA, Trujillo M, Espartero JL, De La Cruz JP (2008) Neuroprotective effect of hydroxytyrosol and hydroxytyrosol acetate in rat brain slices subjected to hypoxia-reoxygenation. Neurosci Lett 446:143–146.  https://doi.org/10.1016/j.neulet.2008.09.022 CrossRefPubMedGoogle Scholar
  103. Gray M, Shirasaki DI, Cepeda C, André VM, Wilburn B, Lu XH, Tao J, Yamazaki I, Li SH, Sun YE, Li XJ, Levine MS, Yang XW (2008) Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J Neurosci 28:6182–6195.  https://doi.org/10.1523/JNEUROSCI.0857-08.2008 CrossRefPubMedPubMedCentralGoogle Scholar
  104. Grote HE, Bull ND, Howard ML, van Dellen A, Blakemore C, Bartlett PF, Hannan AJ (2005) Cognitive disorders and neurogenesis deficits in Huntington’s disease mice are rescued by fluoxetine. Eur J Neurosci 22(8):2081–2088PubMedCrossRefGoogle Scholar
  105. Gu M, Gash MT, Mann VM, Javoy-Agid F, Cooper JM, Schapira AH (1996) Mitochondrial defect in Huntington’s disease caudate nucleus. Ann Neurol 39:385–389.  https://doi.org/10.1002/ana.410390317 CrossRefPubMedGoogle Scholar
  106. Gunawardena S, Her LS, Brusch RG, Laymon RA, Niesman IR, Gordesky-Gold B, Sintasath L, Bonini NM, Goldstein LSB (2003) Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila. Neuron 40:25–40PubMedCrossRefGoogle Scholar
  107. Guo C, Sun L, Chen X, Zhang D (2013) Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res 8:2003–2014.  https://doi.org/10.3969/j.issn.1673-5374.2013.21.009 CrossRefPubMedPubMedCentralGoogle Scholar
  108. Gusella JF, Tanzi RE, Bader PI, Phelan MC, Stevenson R, Hayden MR, Hofman KJ, Faryniarz AG, Gibbons K (1985) Deletion of Huntington’s disease-linked G8 (D4S10) locus in Wolf-Hirschhorn syndrome. Nature 318:75–78PubMedCrossRefGoogle Scholar
  109. Guyot MC, Hantraye P, Dolan R, Palfi S, Maziére M, Brouillet E (1997) Quantifiable bradykinesia, gait abnormalities and Huntington’s disease-like striatal lesions in rats chronically treated with 3-nitropropionic acid. Neuroscience 79:45–56PubMedCrossRefGoogle Scholar
  110. Hagen TM, Ingersoll RT, Lykkesfeldt J, Liu J, Wehr CM, Vinarsky V, Bartholomew JC, Ames AB (1999) (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J 13:411–418PubMedCrossRefGoogle Scholar
  111. Heinsen H, Rüb U, Gangnus D, Jungkunz G, Bauer M, Ulmar G, Bethke B, Schüler M, Böcker F, Eisenmenger W, Götz M, Strik M (1996) Nerve cell loss in the thalamic centromedian-parafascicular complex in patients with Huntington’s disease. Acta Neuropathol 91:161–168PubMedCrossRefGoogle Scholar
  112. Henrotin Y, Priem F, Mobasheri A (2013) Curcumin: a new paradigm and therapeutic opportunity for the treatment of osteoarthritis: curcumin for osteoarthritis management. Springerplus 2:56.  https://doi.org/10.1186/2193-1801-2-56 CrossRefPubMedPubMedCentralGoogle Scholar
  113. Her LS, Goldstein LSB (2008) Enhanced sensitivity of striatal neurons to axonal transport defects induced by mutant huntingtin. J Neurosci 28:13662–13672.  https://doi.org/10.1523/JNEUROSCI.4144-08.2008 CrossRefPubMedGoogle Scholar
  114. Hersch SM, Ferrante RJ (2004) Translating therapies for Huntington’s disease from genetic animal models to clinical trials. NeuroRx 1:298–306PubMedPubMedCentralCrossRefGoogle Scholar
  115. Hersch SM, Gevorkian S, Marder K, Moskowitz C, Feigin A, Cox M, Como P, Zimmerman C, Lin M, Zhang L, Ulug AM, Beal MF, Matson W, Bogdanov M, Ebbel E, Zaleta A, Kaneko Y, Jenkins B, Hevelone N, Zhang H, Yu H, Schoenfeld D, Ferrante R, Rosas HD (2006) Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2’dG. Neurology 66:250–252.  https://doi.org/10.1212/01.wnl.0000194318.74946.b6 CrossRefPubMedGoogle Scholar
  116. Hersch SM, Schifitto G, Oakes D, Bredlau AL, Meyers CM, Nahin R, Rosas HD (2017) The CREST-E study of creatine for Huntington disease. Neurology 89:594–601.  https://doi.org/10.1212/WNL.0000000000004209 CrossRefPubMedPubMedCentralGoogle Scholar
  117. Ho LW, Carmichael J, Swartz J, Wyttenbach A, Rankin J, Rubinsztein DC (2001) The molecular biology of Huntington's disease. Psychol Med 31(1):3–14PubMedCrossRefGoogle Scholar
  118. Hodgson JG, Smith DJ, McCutcheon K, Koide HB, Nishiyama K, Dinulos MB, Stevens ME, Bissada N, Nasir J, Kanazawa I, Disteche CM, Rubin EM, Hayden MR (1996) Human huntingtin derived from YAC transgenes compensates for loss of murine huntingtin by rescue of the embryonic lethal phenotype. Hum Mol Genet 5:1875–1885PubMedCrossRefGoogle Scholar
  119. Hodgson JG, Agopyan N, Gutekunst CA, Leavitt BR, LePiane F, Singaraja R, Smith DJ, Bissada N, McCutcheon K, Nasir J, Jamot L, Li XJ, Stevens ME, Rosemond E, Roder JC, Phillips AG, Rubin EM, Hersch SM, Hayden MR (1999) A YAC mouse model for Huntington’s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 23:181–192PubMedCrossRefGoogle Scholar
  120. Honda T, Honda Y, Favaloro FG, Gribble GW, Suh N, Place AE, Rendi MH, Sporn MB (2002) A novel dicyanotriterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile, active at picomolar concentrations for inhibition of nitric oxide production. Bioorg Med Chem Lett 12:1027–1030PubMedCrossRefGoogle Scholar
  121. Huang F, Ning H, Xin QQ, Huang Y, Wang H, Zhang ZH, Xu DX, Ichihara G, Ye DQ (2009) Melatonin pretreatment attenuates 2-bromopropane-induced testicular toxicity in rats. Toxicology 256:75–82.  https://doi.org/10.1016/j.tox.2008.11.005 CrossRefPubMedGoogle Scholar
  122. Huntington Study Group (2001) A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington’s disease. Neurology 57:397–404Google Scholar
  123. Huntington Study Group Pre2CARE Investigators, Hyson HC, Kieburtz K, Shoulson I, McDermott M, Ravina B, de Blieck EA, Cudkowicz ME, Ferrante RJ, Como P, Frank S, Zimmerman C, Cudkowicz ME, Ferrante K, Newhall K, Jennings D, Kelsey T, Walker F, Hunt V, Daigneault S, Goldstein M, Weber J, Watts A, Beal MF, Browne SE, Metakis LJ (2010) Safety and tolerability of high-dosage coenzyme Q10 in Huntington’s disease and healthy subjects. Mov Disord 25:1924–1928.  https://doi.org/10.1002/mds.22408 CrossRefGoogle Scholar
  124. Iannicola C, Moreno S, Oliverio S, Nardacci R, Ciofi-Luzzatto A, Piacentini M (2000) Early alterations in gene expression and cell morphology in a mouse model of Huntington’s disease. J Neurochem 75:830–839.  https://doi.org/10.1046/j.1471-4159.2000.0750830.x CrossRefPubMedGoogle Scholar
  125. Irwin CC, Wexler NS, Young AB, Ozelius LJ, Penney JB, Shoulson I, Snodgrass SR, Ramos-Arroyo MA, Sanchez-Ramos J, Penchaszadeh GK (1989) The role of mitochondrial DNA in Huntington’s disease. J Mol Neurosci 1:129–136PubMedGoogle Scholar
  126. Jackson GR, Salecker I, Dong X, Yao X, Arnheim N, Faber PW, MacDonald ME, Zipursky SL (1998) Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron 21:633–642PubMedCrossRefGoogle Scholar
  127. Jain D, Gangshettiwar A (2014) Combination of lycopene, quercetin and poloxamer 188 alleviates anxiety and depression in 3-nitropropionic acid-induced Huntington’s disease in rats. J Intercult Ethnopharmacol 3:186–191.  https://doi.org/10.5455/jice.20140903012921 CrossRefPubMedPubMedCentralGoogle Scholar
  128. Jodeiri Farshbaf M, Ghaedi K (2017) Huntington’s disease and mitochondria. Neurotox Res 32:518–529.  https://doi.org/10.1007/s12640-017-9766-1 CrossRefPubMedGoogle Scholar
  129. Johnson MA, Rajan V, Miller CE, Wightman RM (2006) Dopamine release is severely compromised in the R6/2 mouse model of Huntington’s disease. J Neurochem 97:737–746.  https://doi.org/10.1111/j.1471-4159.2006.03762.x CrossRefPubMedGoogle Scholar
  130. Johnson MA, Villanueva M, Haynes CL, Seipel AT, Buhler LA, Wightman RM (2007) Catecholamine exocytosis is diminished in R6/2 Huntington’s disease model mice. J Neurochem 103:2102–2110.  https://doi.org/10.1111/j.1471-4159.2007.04908.x CrossRefPubMedGoogle Scholar
  131. Johri A, Beal MF (2012) Mitochondrial dysfunction in neurodegenerative diseases. J Pharmacol Exp Ther 342:619–630.  https://doi.org/10.1124/jpet.112.192138 CrossRefPubMedPubMedCentralGoogle Scholar
  132. Johri A, Chaturvedi RK, Beal MF (2011) Hugging tight in Huntington’s. Nat Med 17:245–246.  https://doi.org/10.1038/nm0311-245 CrossRefPubMedGoogle Scholar
  133. Joshi PR, Wu NP, André VM, Cummings DM, Cepeda C, Joyce JA, Carroll JB, Leavitt BR, Hayden MR, Levine MS, Bamford NS (2009) Age-dependent alterations of corticostriatal activity in the YAC128 mouse model of Huntington’s disease. J Neurosci 29:2414–2427.  https://doi.org/10.1523/JNEUROSCI.5687-08.2009 CrossRefPubMedPubMedCentralGoogle Scholar
  134. Kassubek J, Juengling FD, Ecker D, Landwehrmeyer GB (2005) Thalamic atrophy in Huntington’s disease co-varies with cognitive performance: a morphometric MRI analysis. Cereb Cortex 15:846–853.  https://doi.org/10.1093/cercor/bhh185 CrossRefPubMedGoogle Scholar
  135. Katsube T, Imawaka N, Kawano Y, Yamazaki Y, Shiwaku K, Yamane Y (2006) Antioxidant flavonol glycosides in mulberry (Morus alba L.) leaves isolated based on LDL antioxidant activity. Food Chem 97:25–31.  https://doi.org/10.1016/j.foodchem.2005.03.019 CrossRefGoogle Scholar
  136. Kieburtz K, Feigin A, McDermott M, Como P, Abwender D, Zimmerman C, Hickey C, Orme C, Claude K, Sotack J, Greenamyre JT, Dunn C, Shoulson I (1996) A controlled trial of remacemide hydrochloride in Huntington’s disease. Mov Disord 11:273–277.  https://doi.org/10.1002/mds.870110310 CrossRefPubMedGoogle Scholar
  137. Kim KH, Lee KW, Kim DY, Park HH, Kwon IB, Lee HJ (2005) Optimal recovery of high-purity rutin crystals from the whole plant of Fagopyrum esculentum Moench (buckwheat) by extraction, fractionation, and recrystallization. Bioresour Technol 96:1709–1712.  https://doi.org/10.1016/j.biortech.2004.12.025 CrossRefPubMedGoogle Scholar
  138. Kim J, Moody JP, Edgerly CK, Bordiuk OL, Cormier K, Smith K, Beal MF, Ferrante RJ (2010) Mitochondrial loss, dysfunction and altered dynamics in Huntington’s disease. Hum Mol Genet 19:3919–3935.  https://doi.org/10.1093/hmg/ddq306 CrossRefPubMedPubMedCentralGoogle Scholar
  139. Klapstein GJ, Fisher RS, Zanjani H, Cepeda C, Jokel ES, Chesselet MF, Levine MS (2001) Electrophysiological and morphological changes in striatal spiny neurons in R6/2 Huntington’s disease transgenic mice. J Neurophysiol 86:2667–2677.  https://doi.org/10.1152/jn.2001.86.6.2667 CrossRefPubMedGoogle Scholar
  140. Kocot J, Luchowska-Kocot D, Kiełczykowska M, Musik I, Kurzepa J (2017) Does vitamin C influence neurodegenerative diseases and psychiatric disorders? Nutrients 9(7):659.  https://doi.org/10.3390/nu9070659 CrossRefPubMedCentralPubMedGoogle Scholar
  141. Koda T, Kuroda Y, Imai H (2008) Protective effect of rutin against spatial memory impairment induced by trimethyltin in rats. Nutr Res 28:629–634.  https://doi.org/10.1016/j.nutres.2008.06.004 CrossRefPubMedGoogle Scholar
  142. Kovacic P, Pozos RS, Somanathan R, Shangari N, O’Brien PJ (2005) Mechanism of mitochondrial uncouplers, inhibitors, and toxins: focus on electron transfer, free radicals, and structure-activity relationships. Curr Med Chem 12:2601–2623.  https://doi.org/10.2174/092986705774370646 CrossRefPubMedGoogle Scholar
  143. Kremer HP, Roos RA, Dingjan G, Marani E, Bots GT (1990) Atrophy of the hypothalamic lateral tuberal nucleus in Huntington’s disease. J Neuropathol Exp Neurol 49:371–382PubMedCrossRefGoogle Scholar
  144. Kumar P, Kumar A (2009) Effect of lycopene and epigallocatechin-3-gallate against 3-nitropropionic acid induced cognitive dysfunction and glutathione depletion in rat: a novel nitric oxide mechanism. Food Chem Toxicol 47:2522–2530.  https://doi.org/10.1016/j.fct.2009.07.011 CrossRefPubMedGoogle Scholar
  145. Kumar P, Kumar A (2010) Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington’s like symptoms in rats: possible role of nitric oxide. Behav Brain Res 206:38–46.  https://doi.org/10.1016/j.bbr.2009.08.028 CrossRefPubMedGoogle Scholar
  146. Kumar A, Ratan RR (2016) Oxidative stress and Huntington’s disease: the good, the bad, and the ugly. J Huntingtons Dis 5:217–237.  https://doi.org/10.3233/JHD-160205 CrossRefPubMedPubMedCentralGoogle Scholar
  147. Kumar P, Kalonia H, Kumar A (2010) Possible nitric oxide modulation in protective effect of FK-506 against 3-nitropropionic acid-induced behavioral, oxidative, neurochemical, and mitochondrial alterations in rat brain. Drug Chem Toxicol 33:377–392.  https://doi.org/10.3109/01480541003642050 CrossRefPubMedGoogle Scholar
  148. Kumar A, Vaish M, Ratan RR (2014) Transcriptional dysregulation in Huntington’s disease: a failure of adaptive transcriptional homeostasis. Drug Discov Today 19:956–962.  https://doi.org/10.1016/j.drudis.2014.03.016 CrossRefPubMedPubMedCentralGoogle Scholar
  149. Laforet GA, Sapp E, Chase K, McIntyre C, Boyce FM, Campbell M, Cadigan BA, Warzecki L, Tagle DA, Reddy PH, Cepeda C, Calvert CR, Jokel ES, Klapstein GJ, Ariano MA, Levine MS, DiFiglia M, Aronin N (2001) Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington’s disease. J Neurosci 21:9112–9123PubMedCrossRefGoogle Scholar
  150. Lawler JM, Barnes WS, Wu G, Song W, Demaree S (2002) Direct antioxidant properties of creatine. Biochem Biophys Res Commun 290:47–52.  https://doi.org/10.1006/bbrc.2001.6164 CrossRefPubMedGoogle Scholar
  151. Lehrmann E, Guidetti P, Löve A, Williamson J, Bertram EH, Schwarcz R (2008) Glial activation precedes seizures and hippocampal neurodegeneration in measles virus–infected mice. Epilepsia 49:13–23.  https://doi.org/10.1111/j.1528-1167.2008.01489.x CrossRefPubMedGoogle Scholar
  152. Li H, Li SH, Yu ZX, Shelbourne P, Li XJ (2001) Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington’s disease mice. J Neurosci 21:8473–8481PubMedCrossRefGoogle Scholar
  153. Li H, Wyman T, Yu ZX, Li SH, Li XJ (2003) Abnormal association of mutant huntingtin with synaptic vesicles inhibits glutamate release. Hum Mol Genet 12:2021–2030.  https://doi.org/10.1093/hmg/ddg218 CrossRefPubMedGoogle Scholar
  154. Liby K, Hock T, Yore MM, Suh N, Place AE, Risingsong R, Williams CR, Royce DB, Honda T, Honda Y, Gribble GW, Hill-Kapturczak N, Agarwal A, Sporn MB (2005) The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling. Cancer Res 65:4789–4798.  https://doi.org/10.1158/0008-5472.CAN-04-4539 CrossRefPubMedGoogle Scholar
  155. Liévens JC, Woodman B, Mahal A, Spasic-Boscovic O, Samuel D, Kerkerian-Le Goff L, Bates GP (2001) Impaired glutamate uptake in the R6 Huntington’s disease transgenic mice. Neurobiol Dis 8:807–821.  https://doi.org/10.1006/nbdi.2001.0430 CrossRefPubMedGoogle Scholar
  156. Lim D, Fedrizzi L, Tartari M, Zuccato C, Cattaneo E, Brini M, Carafoli E (2008) Calcium homeostasis and mitochondrial dysfunction in striatal neurons of Huntington disease. J Biol Chem 283:5780–5789.  https://doi.org/10.1074/jbc.M704704200 CrossRefPubMedGoogle Scholar
  157. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795.  https://doi.org/10.1038/nature05292 CrossRefGoogle Scholar
  158. Lindroos R, Dorst MC, Du K, Filipović M, Keller D, Ketzef M, Kozlov AK, Kumar A, Lindahl M, Nair AG, Pérez-Fernández J, Grillner S, Silberberg G, Hellgren Kotaleski J (2018) Basal ganglia neuromodulation over multiple temporal and structural scales—simulations of direct pathway MSNs investigate the fast onset of dopaminergic effects and predict the role of Kv4.2. Front Neural Circuits 12:3.  https://doi.org/10.3389/fncir.2018.00003 CrossRefPubMedPubMedCentralGoogle Scholar
  159. Lucas DR, Newhouse JP (1957) The toxic effect of sodium L-glutamate on the inner layers of the retina. AMA Arch Ophthalmol 58:193–201PubMedCrossRefGoogle Scholar
  160. Ludolph AC, He F, Spencer PS, Hammerstad J, Sabri M (1991) 3-Nitropropionic acid-exogenous animal neurotoxin and possible human striatal toxin. Can J Neurol Sci 18:492–498PubMedCrossRefPubMedCentralGoogle Scholar
  161. Luthi-Carter R, Strand A, Peters NL, Solano SM, Hollingsworth ZR, Menon AS, Frey AS, Spektor BS, Penney EB, Schilling G, Ross CA, Borchelt DR, Tapscott SJ, Young AB, Cha JH, Olson JM (2000a) Decreased expression of striatal signaling genes in a mouse model of Huntington’s disease. Hum Mol Genet 9:1259–1271PubMedCrossRefGoogle Scholar
  162. Luthi-Carter R, Strand A, Peters NL, Solano SM, Hollingsworth ZR, Menon AS, Frey AS, Spektor BS, Penney EB, Schilling G, Ross CA, Borchelt DR, Tapscott SJ, Young AB, Cha JHJ, Olson JM (2000b) Decreased expression of striatal signaling genes in a mouse model of Huntington’s disease. Hum Mol Genet 9:1259–1271.  https://doi.org/10.1093/hmg/9.9.1259 CrossRefPubMedGoogle Scholar
  163. Majewska MD, Bell JA (1990) Ascorbic acid protects neurons from injury induced by glutamate and NMDA. Neuroreport 1:194–196PubMedCrossRefPubMedCentralGoogle Scholar
  164. Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, Lawton M, Trottier Y, Lehrach H, Davies SW, Bates GP (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87:493–506.  https://doi.org/10.1016/S0092-8674(00)81369-0 CrossRefPubMedGoogle Scholar
  165. Matthews RT, Yang L, Browne S, Baik M, Beal MF (1998) Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Proc Natl Acad Sci U S A 95:8892–8897PubMedPubMedCentralCrossRefGoogle Scholar
  166. May JM, Qu ZC, Mendiratta S (1998) Protection and recycling of alpha-tocopherol in human erythrocytes by intracellular ascorbic acid. Arch Biochem Biophys 349:281–289.  https://doi.org/10.1006/abbi.1997.0473 CrossRefPubMedGoogle Scholar
  167. McGuire JR, Rong J, Li SH, Li XJ (2006) Interaction of Huntingtin-associated protein-1 with kinesin light chain: implications in intracellular trafficking in neurons. J Biol Chem 281:3552–3559.  https://doi.org/10.1074/jbc.M509806200 CrossRefPubMedGoogle Scholar
  168. Meier T, Buyse G (2009) Idebenone: an emerging therapy for Friedreich ataxia. J Neurol 256(1):25–30.  https://doi.org/10.1007/s00415-009-1005-0 CrossRefPubMedGoogle Scholar
  169. Mendiratta S, Qu Z, May JM (1998) Erythrocyte defenses against hydrogen peroxide: the role of ascorbic acid. Biochimica et Biophysica Acta (BBA) 1380:389–395.  https://doi.org/10.1016/S0304-4165(98)00005-1
  170. Miyamoto M, Coyle JT (1990) Idebenone attenuates neuronal degeneration induced by intrastriatal injection of excitotoxins. Exp Neurol 108:38–45.  https://doi.org/10.1016/0014-4886(90)90005-D CrossRefPubMedGoogle Scholar
  171. Montoya A, Price BH, Menear M, Lepage M (2006) Brain imaging and cognitive dysfunctions in Huntington’s disease. J Psychiatry Neurosci 31:21–29PubMedPubMedCentralGoogle Scholar
  172. Morales-Martínez A, Sánchez-Mendoza A, Martínez-Lazcano JC, Pineda-Farías JB, Montes S, El-Hafidi M, Martínez-Gopar PE, Tristán-López L, Pérez-Neri I, Zamorano-Carrillo A, Castro N, Ríos C, Pérez-Severiano F (2017) Essential fatty acid-rich diets protect against striatal oxidative damage induced by quinolinic acid in rats. Nutr Neurosci 20:388–395.  https://doi.org/10.1080/1028415X.2016.1147683 CrossRefPubMedGoogle Scholar
  173. Morton AJ (2013) Circadian and sleep disorder in Huntington’s disease. Exp Neurol 243:34–44.  https://doi.org/10.1016/j.expneurol.2012.10.014 CrossRefPubMedGoogle Scholar
  174. Morton AJ, Howland DS (2013) Large genetic animal models of Huntington’s disease. J Huntington’s Dis 2:3–19.  https://doi.org/10.3233/JHD-130050 CrossRefGoogle Scholar
  175. Morton AJ, Faull RL, Edwardson JM (2001) Abnormalities in the synaptic vesicle fusion machinery in Huntington’s disease. Brain Res Bull 56:111–117PubMedCrossRefGoogle Scholar
  176. Müller L, Caris-Veyrat C, Lowe G, Böhm V (2016) Lycopene and its antioxidant role in the prevention of cardiovascular diseases—a critical review. Crit Rev Food Sci Nutr 56(11):1868–1879.  https://doi.org/10.1080/10408398.2013.801827 CrossRefPubMedGoogle Scholar
  177. Murphy KP, Carter RJ, Lione LA, Mangiarini L, Mahal A, Bates GP, Dunnett SB, Morton AJ (2000) Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington’s disease mutation. J Neurosci 20:5115–5123PubMedCrossRefGoogle Scholar
  178. Nguyen HP, Kobbe P, Rahne H, Wörpel T, Jäger B, Stephan M, Pabst R, Holzmann C, Riess O, Korr H, Kántor O, Petrasch-Parwez E, Wetzel R, Osmand A, von Hörsten S (2006) Behavioral abnormalities precede neuropathological markers in rats transgenic for Huntington’s disease. Hum Mol Genet 15:3177–3194  https://doi.org/10.1093/hmg/ddl394 PubMedCrossRefGoogle Scholar
  179. Nohria V, Vaddadi KS (1982) Tardive dyskinesias and essential fatty acids: an animal model study. In: Horrobin DF (ed) Clinical uses of essential fatty acids. Eden Press, MontrealGoogle Scholar
  180. Ortiz AN, Kurth BJ, Osterhaus GL, Johnson MA (2010) Dysregulation of intracellular dopamine stores revealed in the R6/2 mouse striatum. J Neurochem 112:755–761.  https://doi.org/10.1111/j.1471-4159.2009.06501.x CrossRefPubMedGoogle Scholar
  181. Palfi S, Brouillet E, Jarraya B, Bloch J, Jan C, Shin M, Condé F, Li XJ, Aebischer P, Hantraye P, Déglon N (2007) Expression of mutated huntingtin fragment in the putamen is sufficient to produce abnormal movement in non-human primates. Mol Ther 15:1444–1451.  https://doi.org/10.1038/sj.mt.6300185 CrossRefPubMedGoogle Scholar
  182. Panov AV, Gutekunst CA, Leavitt BR, Hayden MR, Burke JR, Strittmatter WJ, Greenamyre JT (2002) Early mitochondrial calcium defects in Huntington’s disease are a direct effect of polyglutamines. Nat Neurosci 5:731–736.  https://doi.org/10.1038/nn884 CrossRefPubMedGoogle Scholar
  183. Panov AV, Burke JR, Strittmatter WJ, Greenamyre JT (2003) In vitro effects of polyglutamine tracts on Ca2+−dependent depolarization of rat and human mitochondria: relevance to Huntington’s disease. Arch Biochem Biophys 410:1–6PubMedCrossRefGoogle Scholar
  184. Paoletti P, Vila I, Rifé M, Lizcano JM, Alberch J, Ginés S (2008) Dopaminergic and glutamatergic signaling crosstalk in Huntington’s disease neurodegeneration: the role of p25/cyclin-dependent kinase 5. J Neurosci 28:10090–10101.  https://doi.org/10.1523/JNEUROSCI.3237-08.2008 CrossRefPubMedGoogle Scholar
  185. Paulsen JS, Magnotta VA, Mikos AE, Paulson HL, Penziner E, Andreasen NC, Nopoulos PC (2006) Brain structure in preclinical Huntington’s disease. Biol Psychiatry 59:57–63.  https://doi.org/10.1016/j.biopsych.2005.06.003 CrossRefPubMedGoogle Scholar
  186. Petersén A, Castilho RF, Hansson O, Wieloch T, Brundin P (2000) Oxidative stress, mitochondrial permeability transition and activation of caspases in calcium ionophore A23187-induced death of cultured striatal neurons. Brain Res 857:20–29PubMedCrossRefGoogle Scholar
  187. Petersén A, Chase K, Puschban Z, DiFiglia M, Brundin P, Aronin N (2002) Maintenance of susceptibility to neurodegeneration following intrastriatal injections of quinolinic acid in a new transgenic mouse model of Huntington’s disease. Exp Neurol 175:297–300.  https://doi.org/10.1006/exnr.2002.7885 CrossRefPubMedGoogle Scholar
  188. Petersén A, Gil J, Maat-Schieman MLC, Björkqvist M, Tanila H, Araújo IM, Smith R, Popovic N, Wierup N, Norlén P, Li JY, Roos RAC, Sundler F, Mulder H, Brundin P (2005) Orexin loss in Huntington’s disease. Hum Mol Genet 14:39–47.  https://doi.org/10.1093/hmg/ddi004 CrossRefPubMedGoogle Scholar
  189. Phillips O, Squitieri F, Sanchez-Castaneda C, Elifani F, Griguoli A, Maglione V, Caltagirone C, Sabatini U, Di Paola M (2015) The corticospinal tract in Huntington’s disease. Cereb Cortex 25(9):2670–2682.  https://doi.org/10.1093/cercor/bhu065 CrossRefPubMedGoogle Scholar
  190. Phom L, Achumi B, Alone DP, Muralidhara YSC (2014) Curcumin’s neuroprotective efficacy in Drosophila model of idiopathic Parkinson’s disease is phase specific: implication of its therapeutic effectiveness. Rejuvenation Res 17:481–489.  https://doi.org/10.1089/rej.2014.1591 CrossRefPubMedPubMedCentralGoogle Scholar
  191. Piccini P (2004) Neurodegenerative movement disorders: the contribution of functional imaging. Curr Opin Neurol 17:459–466PubMedCrossRefGoogle Scholar
  192. Pickrell AM, Youle RJ (2015) The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron 85:257–273.  https://doi.org/10.1016/j.neuron.2014.12.007 CrossRefPubMedPubMedCentralGoogle Scholar
  193. Polyzos A, Holt A, Brown C, Cosme C, Wipf P, Gomez-Marin A, Castro MR, Ayala-Peña S, McMurray CT (2016) Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes. Hum Mol Genet 25:1792–1802.  https://doi.org/10.1093/hmg/ddw051 CrossRefPubMedPubMedCentralGoogle Scholar
  194. Portera-Cailliau C, Hedreen JC, Price DL, Koliatsos VE (1995) Evidence for apoptotic cell death in Huntington disease and excitotoxic animal models. J Neurosci 15:3775–3787PubMedCrossRefGoogle Scholar
  195. Pouladi MA, Stanek LM, Xie Y, Franciosi S, Southwell AL, Deng Y, Butland S, Zhang W, Cheng SH, Shihabuddin LS, Hayden MR (2012) Marked differences in neurochemistry and aggregates despite similar behavioural and neuropathological features of Huntington disease in the full-length BACHD and YAC128 mice. Hum Mol Genet 21:2219–2232.  https://doi.org/10.1093/hmg/dds037 CrossRefPubMedGoogle Scholar
  196. Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N (2012) The incidence and prevalence of Huntington’s disease: a systematic review and meta-analysis. Mov Disord 27:1083–1091.  https://doi.org/10.1002/mds.25075 CrossRefPubMedGoogle Scholar
  197. Puranam KL, Wu G, Strittmatter WJ, Burke JR (2006) Polyglutamine expansion inhibits respiration by increasing reactive oxygen species in isolated mitochondria. Biochem Biophys Res Commun 341:607–613.  https://doi.org/10.1016/j.bbrc.2006.01.007 CrossRefPubMedGoogle Scholar
  198. Quiles JL, Ochoa JJ, Ramirez-Tortosa C, Battino M, Huertas JR, Martín Y, Mataix J (2004) Dietary fat type (virgin olive vs. sunflower oils) affects age-related changes in DNA double-strand-breaks, antioxidant capacity and blood lipids in rats. Exp Gerontol 39:1189–1198.  https://doi.org/10.1016/j.exger.2004.05.002 CrossRefPubMedGoogle Scholar
  199. Quintanilla RA, Johnson GVW (2009) Role of mitochondrial dysfunction in the pathogenesis of Huntington’s disease. Brain Res Bull 80:242–247.  https://doi.org/10.1016/j.brainresbull.2009.07.010 CrossRefPubMedPubMedCentralGoogle Scholar
  200. Quinti L, Casale M, Moniot S, Pais TF, Van Kanegan MJ, Kaltenbach LS, Pallos J, Lim RG, Naidu SD, Runne H, Meisel L, Rauf NA, Leyfer D, Maxwell MM, Saiah E, Landers JE, Luthi-Carter R, Abagyan R, Dinkova-Kostova AT, Steegborn C, Marsh JL, Lo DC, Thompson LM, Kazantsev AG (2016) SIRT2- and NRF2-targeting thiazole-containing compound with therapeutic activity in Huntington’s disease models. Cell Chem Biol 23:849–861.  https://doi.org/10.1016/j.chembiol.2016.05.015 CrossRefPubMedGoogle Scholar
  201. Ramaswamy S, McBride JL, Kordower JH (2007) Animal models of Huntington’s disease. ILAR J 48:356–373PubMedCrossRefGoogle Scholar
  202. Ranen NG, Peyser CE, Coyle JT, Bylsma FW, Sherr M, Day L, Folstein MF, Brandt J, Ross CA, Folstein SE (1996) A controlled trial of idebenone in Huntington’s disease. Mov Disord 11:549–554.  https://doi.org/10.1002/mds.870110510 CrossRefPubMedGoogle Scholar
  203. Ransome MI, Renoir T, Hannan AJ (2012) Hippocampal neurogenesis, cognitive deficits and affective disorder in Huntington’s disease. Neural Plasticity 7.  https://doi.org/10.1155/2012/874387
  204. Ratovitski T, Chighladze E, Arbez N, Boronina T, Herbrich S, Cole RN, Ross CA (2012) Huntingtin protein interactions altered by polyglutamine expansion as determined by quantitative proteomic analysis. Cell Cycle 11:2006–2021.  https://doi.org/10.4161/cc.20423 CrossRefPubMedPubMedCentralGoogle Scholar
  205. Rawlins MD, Wexler NS, Wexler AR, Tabrizi SJ, Douglas I, Evans SJW, Smeeth L (2016) The prevalence of Huntington’s disease. Neuroepidemiology 46:144–153.  https://doi.org/10.1159/000443738 CrossRefPubMedGoogle Scholar
  206. Raymond LA, André VM, Cepeda C, Gladding CM, Milnerwood AJ, Levine MS (2011) Pathophysiology of Huntington’s disease: time-dependent alterations in synaptic and receptor function. Neuroscience 198:252–273.  https://doi.org/10.1016/j.neuroscience.2011.08.052 CrossRefPubMedPubMedCentralGoogle Scholar
  207. Rebec GV, Barton SJ, Ennis MD (2002) Dysregulation of ascorbate release in the striatum of behaving mice expressing the Huntington’s disease gene. J Neurosci 22:202CrossRefGoogle Scholar
  208. Rebec GV, Barton SJ, Marseilles AM, Collins K (2003) Ascorbate treatment attenuates the Huntington behavioral phenotype in mice. Neuroreport 14:1263–1265.  https://doi.org/10.1097/01.wnr.0000081868.45938.12 CrossRefPubMedGoogle Scholar
  209. Reddy PH, Williams M, Charles V, Garrett L, Pike-Buchanan L, Whetsell WO, Miller G, Tagle DA (1998) Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nat Genet 20:198–202.  https://doi.org/10.1038/2510 CrossRefPubMedGoogle Scholar
  210. Reiner A, Albin RL, Anderson KD, D’Amato CJ, Penney JB, Young AB (1988) Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci U S A 85:5733–5737PubMedPubMedCentralCrossRefGoogle Scholar
  211. Reiner A, Shelby E, Wang H, Demarch Z, Deng Y, Guley NH, Hogg V, Roxburgh R, Tippett LJ, Waldvogel HJ, Faull RLM (2013) Striatal parvalbuminergic neurons are lost in Huntington’s disease: implications for dystonia. Mov Disord 28:1691–1699.  https://doi.org/10.1002/mds.25624 CrossRefPubMedPubMedCentralGoogle Scholar
  212. Ribeiro FM, Paquet M, Ferreira LT, Cregan T, Swan P, Cregan SP, Ferguson SSG (2010) Metabotropic glutamate receptor-mediated cell signaling pathways are altered in a mouse model of Huntington’s disease. J Neurosci 30:316–324.  https://doi.org/10.1523/JNEUROSCI.4974-09.2010 CrossRefPubMedGoogle Scholar
  213. Richard D, Kefi K, Barbe U, Bausero P, Visioli F (2008) Polyunsaturated fatty acids as antioxidants. Pharmacol Res 57:451–455.  https://doi.org/10.1016/j.phrs.2008.05.002 CrossRefPubMedGoogle Scholar
  214. Rigamonti D, Bauer JH, De-Fraja C, Conti L, Sipione S, Sciorati C, Clementi E, Hackam A, Hayden MR, Li Y, Cooper JK, Ross CA, Govoni S, Vincenz C, Cattaneo E (2000) Wild-type huntingtin protects from apoptosis upstream of caspase-3. J Neurosci 20:3705–3713PubMedCrossRefGoogle Scholar
  215. Rigamonti D, Sipione S, Goffredo D, Zuccato C, Fossale E, Cattaneo E (2001) Huntingtin’s neuroprotective activity occurs via inhibition of procaspase-9 processing. J Biol Chem 276:14545–14548.  https://doi.org/10.1074/jbc.C100044200 CrossRefPubMedGoogle Scholar
  216. Rosas HD, Koroshetz WJ, Chen YI, Skeuse C, Vangel M, Cudkowicz ME, Caplan K, Marek K, Seidman LJ, Makris N, Jenkins BG, Goldstein JM (2003) Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis. Neurology 60:1615–1620PubMedCrossRefGoogle Scholar
  217. Rosenstock TR, de Brito OM, Lombardi V, Louros S, Ribeiro M, Almeida S, Ferreira IL, Oliveira CR, Rego AC (2011) FK506 ameliorates cell death features in Huntington’s disease striatal cell models. Neurochem Int 59:600–609.  https://doi.org/10.1016/j.neuint.2011.04.009 CrossRefPubMedGoogle Scholar
  218. Rubinsztein DC, Carmichael J (2003) Huntington’s disease: molecular basis of neurodegeneration. Expert Rev Mol Med 5:1–21.  https://doi.org/10.1017/S1462399403006549 CrossRefPubMedGoogle Scholar
  219. Saki M, Prakash A (2017) DNA damage related crosstalk between the nucleus and mitochondria. Free Radic Biol Med 107:216–227.  https://doi.org/10.1016/j.freeradbiomed.2016.11.050 CrossRefPubMedGoogle Scholar
  220. Samuni Y, Goldstein S, Dean OM, Berk M (2013) The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta 1830:4117–4129.  https://doi.org/10.1016/j.bbagen.2013.04.016 CrossRefPubMedGoogle Scholar
  221. Sandhir R, Sood A, Mehrotra A, Kamboj SS (2012) N-Acetylcysteine reverses mitochondrial dysfunctions and behavioral abnormalities in 3-nitropropionic acid-induced Huntington’s disease. Neurodegener Dis 9:145–157.  https://doi.org/10.1159/000334273 CrossRefPubMedGoogle Scholar
  222. Santamaría A, Salvatierra-Sánchez R, Vázquez-Román B, Santiago-López D, Villeda-Hernández J, Galván-Arzate S, Jiménez-Capdeville ME, Ali SF (2003) Protective effects of the antioxidant selenium on quinolinic acid-induced neurotoxicity in rats: in vitro and in vivo studies. J Neurochem 86:479–488PubMedCrossRefGoogle Scholar
  223. Sawa A, Wiegand GW, Cooper J, Margolis RL, Sharp AH, Lawler JF, Greenamyre JT, Snyder SH, Ross CA (1999) Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization. Nat Med 5:1194–1198.  https://doi.org/10.1038/13518 CrossRefPubMedGoogle Scholar
  224. Schilling G, Becher MW, Sharp AH, Jinnah HA, Duan K, Kotzuk JA, Slunt HH, Ratovitski T, Cooper JK, Jenkins NA, Copeland NG, Price DL, Ross CA, Borchelt DR (1999) Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum Mol Genet 8:397–407PubMedCrossRefGoogle Scholar
  225. Schilling G, Coonfield ML, Ross CA, Borchelt DR (2001) Coenzyme Q10 and remacemide hydrochloride ameliorate motor deficits in a Huntington’s disease transgenic mouse model. Neurosci Lett 315:149–153PubMedCrossRefGoogle Scholar
  226. Schulz KF, Chalmers I, Hayes RJ, Altman DG (1995) Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 273:408–412PubMedCrossRefGoogle Scholar
  227. Schwab LC, Garas SN, Drouin-Ouellet J, Mason SL, Stott SR, Barker RA (2015) Dopamine and Huntington’s disease. Expert Rev Neurother 15:445–458.  https://doi.org/10.1586/14737175.2015.1025383 CrossRefPubMedGoogle Scholar
  228. Scrimgeour EM (2009) Huntington disease (chorea) in the Middle East. Sultan Qaboos Univ Med J 9:16–23PubMedPubMedCentralGoogle Scholar
  229. Shear DA, Haik KL, Dunbar GL (2000) Creatine reduces 3-nitropropionic-acid-induced cognitive and motor abnormalities in rats. Neuroreport 11:1833–1837PubMedCrossRefGoogle Scholar
  230. Shin JY, Fang ZH, Yu ZX, Wang CE, Li SH, Li XJ (2005) Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol 171:1001–1012.  https://doi.org/10.1083/jcb.200508072 CrossRefPubMedPubMedCentralGoogle Scholar
  231. Shirendeb U, Reddy AP, Manczak M, Calkins MJ, Mao P, Tagle DA, Reddy PH (2011) Abnormal mitochondrial dynamics, mitochondrial loss and mutant huntingtin oligomers in Huntington’s disease: implications for selective neuronal damage. Hum Mol Genet 20:1438–1455.  https://doi.org/10.1093/hmg/ddr024 CrossRefPubMedPubMedCentralGoogle Scholar
  232. Singh S, Kumar P (2016) Neuroprotective activity of curcumin in combination with piperine against quinolinic acid induced neurodegeneration in rats. Pharmacology 97:151–160.  https://doi.org/10.1159/000443896 CrossRefPubMedGoogle Scholar
  233. Sipione S, Rigamonti D, Valenza M, Zuccato C, Conti L, Pritchard J, Kooperberg C, Olson JM, Cattaneo E (2002) Early transcriptional profiles in huntingtin-inducible striatal cells by microarray analyses. Hum Mol Genet 11:1953–1965PubMedCrossRefGoogle Scholar
  234. Slow EJ, van Raamsdonk J, Rogers D, Coleman SH, Graham RK, Deng Y, Oh R, Bissada N, Hossain SM, Yang YZ, Li XJ, Simpson EM, Gutekunst CA, Leavitt BR, Hayden MR (2003) Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum Mol Genet 12:1555–1567PubMedCrossRefGoogle Scholar
  235. Smith R, Klein P, Koc-Schmitz Y, Waldvogel HJ, Faull RLM, Brundin P, Plomann M, Li JY (2007) Loss of SNAP-25 and rabphilin 3a in sensory-motor cortex in Huntington’s disease. J Neurochem 103:115–123.  https://doi.org/10.1111/j.1471-4159.2007.04703.x CrossRefPubMedGoogle Scholar
  236. Solovyev ND (2015) Importance of selenium and selenoprotein for brain function: from antioxidant protection to neuronal signalling. J Inorg Biochem 153:1–12.  https://doi.org/10.1016/j.jinorgbio.2015.09.003 CrossRefPubMedGoogle Scholar
  237. Song I, Huganir RL (2002) Regulation of AMPA receptors during synaptic plasticity. Trends Neurosci 25:578–588PubMedCrossRefGoogle Scholar
  238. Song W, Chen J, Petrilli A, Liot G, Klinglmayr E, Zhou Y, Poquiz P, Tjong J, Pouladi MA, Hayden MR, Masliah E, Ellisman M, Rouiller I, Schwarzenbacher R, Bossy B, Perkins G, Bossy-Wetzel E (2011) Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity. Nat Med 17:377–382.  https://doi.org/10.1038/nm.2313 CrossRefPubMedPubMedCentralGoogle Scholar
  239. Sorolla MA, Reverter-Branchat G, Tamarit J, Ferrer I, Ros J, Cabiscol E (2008) Proteomic and oxidative stress analysis in human brain samples of Huntington disease. Free Radic Biol Med 45:667–678.  https://doi.org/10.1016/j.freeradbiomed.2008.05.014 CrossRefPubMedGoogle Scholar
  240. Sorolla MA, Rodríguez-Colman MJ, Tamarit J, Ortega Z, Lucas JJ, Ferrer I, Ros J, Cabiscol E (2010) Protein oxidation in Huntington disease affects energy production and vitamin B6 metabolism. Free Radic Biol Med 49:612–621.  https://doi.org/10.1016/j.freeradbiomed.2010.05.016 CrossRefPubMedGoogle Scholar
  241. Soto C (2003) Unfolding the role of protein misfolding in neurodegenerative diseases. Nat Rev Neurosci 4:49–60.  https://doi.org/10.1038/nrn1007 CrossRefPubMedGoogle Scholar
  242. Squitieri F, Cannella M, Sgarbi G, Maglione V, Falleni A, Lenzi P, Baracca A, Cislaghi G, Saft C, Ragona G, Russo MA, Thompson LM, Solaini G, Fornai F (2006) Severe ultrastructural mitochondrial changes in lymphoblasts homozygous for Huntington disease mutation. Mech Ageing Dev 127:217–220.  https://doi.org/10.1016/j.mad.2005.09.010 CrossRefPubMedGoogle Scholar
  243. Stack EC, Kubilus JK, Smith K, Cormier K, Del Signore SJ, Guelin E, Ryu H, Hersch SM, Ferrante RJ (2005) Chronology of behavioral symptoms and neuropathological sequela in R6/2 Huntington’s disease transgenic mice. J Comp Neurol 490:354–370.  https://doi.org/10.1002/cne.20680 CrossRefPubMedGoogle Scholar
  244. Stack C, Ho D, Wille E, Calingasan NY, Williams C, Liby K, Sporn M, Dumont M, Beal MF (2010) Triterpenoids CDDO-ethyl amide and CDDO-trifluoroethyl amide improve the behavioral phenotype and brain pathology in a transgenic mouse model of Huntington’s disease. Free Radic Biol Med 49:147–158.  https://doi.org/10.1016/j.freeradbiomed.2010.03.017 CrossRefPubMedPubMedCentralGoogle Scholar
  245. Stahl WL, Swanson PD (1974) Biochemical abnormalities in Huntington’s chorea brains. Neurology 24:813–819PubMedCrossRefGoogle Scholar
  246. Stefani GP, Nunes RB, Dornelles AZ, Alves JP, Piva MO, Domenico MD, Rhoden CR, Lago PD (2014) Effects of creatine supplementation associated with resistance training on oxidative stress in different tissues of rats. J Int Soc Sports Nutr 11(1):11.  https://doi.org/10.1186/1550-2783-11-11 CrossRefPubMedPubMedCentralGoogle Scholar
  247. Suganya SN, Sumathi T (2014) Rutin attenuates 3-nitropropionic acid induced behavioural alterations and mitochondrial dysfunction in the striatum of rat brain. World J Pharm Pharm Sci 4(1):1080–1092Google Scholar
  248. Suganya SN, Sumathi T (2017) Effect of rutin against a mitochondrial toxin, 3-nitropropionicacid induced biochemical, behavioral and histological alterations-a pilot study on Huntington’s disease model in rats. Metab Brain Dis 32:471–481.  https://doi.org/10.1007/s11011-016-9929-4 CrossRefPubMedGoogle Scholar
  249. Suh N, Wang Y, Honda T, Gribble GW, Dmitrovsky E, Hickey WF, Maue RA, Place AE, Porter DM, Spinella MJ, Williams CR, Wu G, Dannenberg AJ, Flanders KC, Letterio JJ, Mangelsdorf DJ, Nathan CF, Nguyen L, Porter WW, Ren RF, Roberts AB, Roche NS, Subbaramaiah K, Sporn MB (1999) A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, with potent differentiating, antiproliferative, and anti-inflammatory activity. Cancer Res 59:336–341PubMedGoogle Scholar
  250. Sun Z, Chen Q, Reiner A (2003) Enkephalinergic striatal projection neurons become less affected by quinolinic acid than substance P-containing striatal projection neurons as rats age. Exp Neurol 184:1034–1042.  https://doi.org/10.1016/j.expneurol.2003.08.016 CrossRefPubMedGoogle Scholar
  251. Szebenyi G, Morfini GA, Babcock A, Gould M, Selkoe K, Stenoien DL, Young M, Faber PW, MacDonald ME, McPhaul MJ, Brady ST (2003) Neuropathogenic forms of huntingtin and androgen receptor inhibit fast axonal transport. Neuron 40:41–52PubMedCrossRefGoogle Scholar
  252. Tabrizi SJ, Cleeter MW, Xuereb J, Taanman JW, Cooper JM, Schapira AH (1999) Biochemical abnormalities and excitotoxicity in Huntington’s disease brain. Ann Neurol 45:25–32PubMedCrossRefGoogle Scholar
  253. Tabrizi SJ, Blamire AM, Manners DN, Rajagopalan B, Styles P, Schapira AHV, Warner TT (2003) Creatine therapy for Huntington’s disease: clinical and MRS findings in a 1-year pilot study. Neurology 61:141–142PubMedCrossRefGoogle Scholar
  254. Tabrizi SJ, Blamire AM, Manners DN, Rajagopalan B, Styles P, Schapira AHV, Warner TT (2005) High-dose creatine therapy for Huntington disease: a 2-year clinical and MRS study. Neurology 64:1655–1656.  https://doi.org/10.1212/01.WNL.0000160388.96242.77 CrossRefPubMedGoogle Scholar
  255. Tang TS, Chen X, Liu J, Bezprozvanny I (2007) Dopaminergic signaling and striatal neurodegeneration in Huntington’s disease. J Neurosci 27:7899–7910.  https://doi.org/10.1523/JNEUROSCI.1396-07.2007 CrossRefPubMedPubMedCentralGoogle Scholar
  256. Tapia E, Soto V, Ortiz-Vega KM, Zarco-Márquez G, Molina-Jijón E, Cristóbal-García M, Santamaría J, García-Niño WR, Correa F, Zazueta C, Pedraza-Chaverri J (2012) Curcumin induces Nrf2 nuclear translocation and prevents glomerular hypertension, hyperfiltration, oxidant stress, and the decrease in antioxidant enzymes in 5/6 nephrectomized rats. Oxidative Med Cell Longev 2012.  https://doi.org/10.1155/2012/269039
  257. Tarnopolsky MA, Beal MF (2001) Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol 49:561–574PubMedCrossRefGoogle Scholar
  258. Tasset I, Sánchez F, Túnez I (2009) The molecular bases of Huntington’s disease: the role played by oxidative stress. Rev Neurol 49:424–429PubMedGoogle Scholar
  259. Tellez-Nagel I, Johnson AB, Terry RD (1974) Studies on brain biopsies of patients with Huntington’s chorea. J Neuropathol Exp Neurol 33:308–332PubMedCrossRefGoogle Scholar
  260. The Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72:971–983CrossRefGoogle Scholar
  261. Thimmulappa RK, Scollick C, Traore K, Yates M, Trush MA, Liby KT, Sporn MB, Yamamoto M, Kensler TW, Biswal S (2006) Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem Biophys Res Commun 351:883–889.  https://doi.org/10.1016/j.bbrc.2006.10.102 CrossRefPubMedPubMedCentralGoogle Scholar
  262. Thu DCV, Oorschot DE, Tippett LJ, Nana AL, Hogg VM, Synek BJ, Luthi-Carter R, Waldvogel HJ, Faull RLM (2010) Cell loss in the motor and cingulate cortex correlates with symptomatology in Huntington’s disease. Brain 133:1094–1110.  https://doi.org/10.1093/brain/awq047 CrossRefPubMedGoogle Scholar
  263. Trushina E, McMurray CT (2007) Oxidative stress and mitochondrial dysfunction in neurodegenerative diseases. Neuroscience 145:1233–1248.  https://doi.org/10.1016/j.neuroscience.2006.10.056 CrossRefPubMedGoogle Scholar
  264. Trushina E, Dyer RB, Badger JD, Ure D, Eide L, Tran DD, Vrieze BT, Legendre-Guillemin V, McPherson PS, Mandavilli BS, Van Houten B, Zeitlin S, McNiven M, Aebersold R, Hayden M, Parisi JE, Seeberg E, Dragatsis I, Doyle K, Bender A, Chacko C, McMurray CT (2004) Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol Cell Biol 24:8195–8209.  https://doi.org/10.1128/MCB.24.18.8195-8209.2004 CrossRefPubMedPubMedCentralGoogle Scholar
  265. Túnez I, Montilla P, Del Carmen Muñoz M, Feijóo M, Salcedo M (2004) Protective effect of melatonin on 3-nitropropionic acid-induced oxidative stress in synaptosomes in an animal model of Huntington’s disease. J Pineal Res 37:252–256.  https://doi.org/10.1111/j.1600-079X.2004.00163.x CrossRefPubMedGoogle Scholar
  266. Túnez I, Sánchez-López F, Agüera E, Fernández-Bolaños R, Sánchez FM, Tasset-Cuevas I (2011) Important role of oxidative stress biomarkers in Huntington’s disease. J Med Chem 54:5602–5606.  https://doi.org/10.1021/jm200605a CrossRefPubMedGoogle Scholar
  267. Vaddadi KS (1992) Use of gamma-linolenic acid in the treatment of schizophrenia and tardive dyskinesia. Prostaglandins Leukot Essent Fatty Acids 46:67–70PubMedCrossRefGoogle Scholar
  268. Vaddadi KS, Soosai E, Chiu E, Dingjan P (2002) A randomised, placebo-controlled, double blind study of treatment of Huntington’s disease with unsaturated fatty acids. NeuroReport 13:29PubMedCrossRefGoogle Scholar
  269. van Duijn E, Kingma EM, van der Mast RC (2007) Psychopathology in verified Huntington’s disease gene carriers. J Neuropsychiatry Clin Neurosci 19:441–448.  https://doi.org/10.1176/jnp.2007.19.4.441 CrossRefPubMedGoogle Scholar
  270. Van Raamsdonk JM, Pearson J, Rogers DA, Bissada N, Vogl AW, Hayden MR, Leavitt BR (2005) Loss of wild-type huntingtin influences motor dysfunction and survival in the YAC128 mouse model of Huntington disease. Hum Mol Genet 14:1379–1392.  https://doi.org/10.1093/hmg/ddi147 CrossRefPubMedGoogle Scholar
  271. Verbessem P, Lemiere J, Eijnde BO, Swinnen S, Vanhees L, Van Leemputte M, Hespel P, Dom R (2003) Creatine supplementation in Huntington’s disease: a placebo-controlled pilot trial. Neurology 61:925–930PubMedCrossRefGoogle Scholar
  272. von Hörsten S, Schmitt I, Nguyen HP, Holzmann C, Schmidt T, Walther T, Bader M, Pabst R, Kobbe P, Krotova J, Stiller D, Kask A, Vaarmann A, Rathke-Hartlieb S, Schulz JB, Grasshoff U, Bauer I, Vieira-Saecker AMM, Paul M, Jones L, Lindenberg KS, Landwehrmeyer B, Bauer A, Li XJ, Riess O (2003) Transgenic rat model of Huntington’s disease. Hum Mol Genet 12:617–624CrossRefGoogle Scholar
  273. Vonsattel JP, DiFiglia M (1998) Huntington disease. J Neuropathol Exp Neurol 57:369–384PubMedCrossRefGoogle Scholar
  274. Wagster MV, Hedreen JC, Peyser CE, Folstein SE, Ross CA (1994) Selective loss of [3H] kainic acid and [3H] AMPA binding in layer VI of frontal cortex in Huntington’s disease. Exp Neurol 127:70–75.  https://doi.org/10.1006/exnr.1994.1081 CrossRefPubMedGoogle Scholar
  275. Walker FO (2007a) Huntington’s disease. Lancet 369:218–228.  https://doi.org/10.1016/S0140-6736(07)60111-1 CrossRefPubMedGoogle Scholar
  276. Walker FO (2007b) Huntington’s disease. Lancet 369:218–228.  https://doi.org/10.1016/S0140-6736(07)60111-1 CrossRefPubMedGoogle Scholar
  277. Wang CJ, Hu CP, Xu KP, Yuan Q, Li FS, Zou H, Tan GS, Li YJ (2010) Protective effect of selaginellin on glutamate-induced cytotoxicity and apoptosis in differentiated PC12 cells. Naunyn Schmiedeberg's Arch Pharmacol 381:73–81.  https://doi.org/10.1007/s00210-009-0470-4 CrossRefGoogle Scholar
  278. Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, Rice S, Steen J, LaVoie MJ, Schwarz TL (2011) PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 147:893–906.  https://doi.org/10.1016/j.cell.2011.10.018 CrossRefPubMedPubMedCentralGoogle Scholar
  279. Wilson JX, Peters CE, Sitar SM, Daoust P, Gelb AW (2000) Glutamate stimulates ascorbate transport by astrocytes. Brain Res 858:61–66PubMedCrossRefGoogle Scholar
  280. Wipf P, Xiao J, Jiang J, Belikova NA, Tyurin VA, Fink MP, Kagan VE (2005) Mitochondrial targeting of selective electron scavengers: synthesis and biological analysis of hemigramicidin-TEMPO conjugates. J Am Chem Soc 127:12460–12461.  https://doi.org/10.1021/ja053679l CrossRefPubMedGoogle Scholar
  281. Wood JD, MacMillan JC, Harper PS, Lowenstein PR, Jones AL (1996) Partial characterisation of murine huntingtin and apparent variations in the subcellular localisation of huntingtin in human. Mouse and Rat Brain Hum Mol Genet 5:481–487.  https://doi.org/10.1093/hmg/5.4.481 CrossRefPubMedGoogle Scholar
  282. Wright DJ, Gray LJ, Finkelstein DI, Crouch PJ, Pow D, Pang TY, Li S, Smith ZM, Francis PS, Renoir T, Hannan AJ (2016) N-acetylcysteine modulates glutamatergic dysfunction and depressive behavior in Huntington’s disease. Hum Mol Genet 25:2923–2933.  https://doi.org/10.1093/hmg/ddw144 CrossRefPubMedGoogle Scholar
  283. Wyttenbach A, Sauvageot O, Carmichael J, Diaz-Latoud C, Arrigo AP, Rubinsztein DC (2002) Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin. Hum Mol Genet 11:1137–1151PubMedCrossRefPubMedCentralGoogle Scholar
  284. Xun Z, Rivera-Sánchez S, Ayala-Peña S, Lim J, Budworth H, Skoda EM, Robbins PD, Niedernhofer LJ, Wipf P, McMurray CT (2012) Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of Huntington’s disease. Cell Rep 2:1137–1142.  https://doi.org/10.1016/j.celrep.2012.10.001 CrossRefPubMedPubMedCentralGoogle Scholar
  285. Yang L, Calingasan NY, Wille EJ, Cormier K, Smith K, Ferrante RJ, Beal MF (2009) Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson’s and Huntington’s diseases. J Neurochem 109:1427–1439.  https://doi.org/10.1111/j.1471-4159.2009.06074.x CrossRefPubMedPubMedCentralGoogle Scholar
  286. Yates MS, Tauchi M, Katsuoka F, Flanders KC, Liby KT, Honda T, Gribble GW, Johnson DA, Johnson JA, Burton NC, Guilarte TR, Yamamoto M, Sporn MB, Kensler TW (2007) Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genes. Mol Cancer Ther 6:154–162.  https://doi.org/10.1158/1535-7163.MCT-06-0516 CrossRefPubMedGoogle Scholar
  287. Young AB, Greenamyre JT, Hollingsworth Z, Albin R, D’Amato C, Shoulson I, Penney JB (1988) NMDA receptor losses in putamen from patients with Huntington’s disease. Science 241:981–983PubMedCrossRefGoogle Scholar
  288. Young JM, Florkowski CM, Molyneux SL, McEwan RG, Frampton CM, George PM, Scott RS (2007) Effect of coenzyme Q(10) supplementation on simvastatin-induced myalgia. Am J Cardiol 100:1400–1403.  https://doi.org/10.1016/j.amjcard.2007.06.03 CrossRefPubMedGoogle Scholar
  289. Zhang Y, Leavitt BR, van Raamsdonk JM, Dragatsis I, Goldowitz D, MacDonald ME, Hayden MR, Friedlander RM (2006) Huntingtin inhibits caspase-3 activation. EMBO J 25:5896–5906.  https://doi.org/10.1038/sj.emboj.7601445 CrossRefPubMedPubMedCentralGoogle Scholar
  290. Zhang M, An C, Gao Y, Leak RK, Chen J, Zhang F (2013) Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection. Prog Neurobiol 100:30–47.  https://doi.org/10.1016/j.pneurobio.2012.09.003 CrossRefPubMedGoogle Scholar
  291. Zuccato C, Cattaneo E (2007) Role of brain-derived neurotrophic factor in Huntington’s disease. Prog Neurobiol 81:294–330.  https://doi.org/10.1016/j.pneurobio.2007.01.003 CrossRefPubMedGoogle Scholar
  292. Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, Cataudella T, Leavitt BR, Hayden MR, Timmusk T, Rigamonti D, Cattaneo E (2003) Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet 35:76–83.  https://doi.org/10.1038/ng1219 CrossRefPubMedGoogle Scholar
  293. Zuccato C, Valenza M, Cattaneo E (2010) Molecular mechanisms and potential therapeutical targets in Huntington’s disease. Physiol Rev 90:905–981.  https://doi.org/10.1152/physrev.00041.2009 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Musthafa Mohamed Essa
    • 1
    • 2
  • Marzieh Moghadas
    • 3
  • Taher Ba-Omar
    • 3
  • M. Walid Qoronfleh
    • 4
  • Gilles J. Guillemin
    • 5
  • Thamilarasan Manivasagam
    • 6
  • Arokiasamy Justin-Thenmozhi
    • 6
  • Bipul Ray
    • 7
  • Abid Bhat
    • 7
  • Saravana Babu Chidambaram
    • 7
  • Amanda J Fernandes
    • 8
  • Byoung-Joon Song
    • 9
  • Mohammed Akbar
    • 9
  1. 1.Department of Food Science and Nutrition, College of Agricultural and Marine SciencesSultan Qaboos UniversityMuscatOman
  2. 2.Ageing and Dementia Research groupSultan Qaboos UniversityMuscatOman
  3. 3.Department of Biology, College of ScienceSultan Qaboos UniversityMuscatOman
  4. 4.Research & Policy Department, World Innovation Summit for Health (WISH)Qatar FoundationDohaQatar
  5. 5.Department of Biomedical Sciences, Faculty of Medicine and Health SciencesMacquarie UniversitySydneyAustralia
  6. 6.Department of Biochemistry, Faculty of ScienceAnnamalai UniversityChidambaramIndia
  7. 7.Department of Pharmacology, JSS College of PharmacyJSS Academy of Higher Education and ResearchMysoreIndia
  8. 8.Department of BiotechnologyManipal Institute of TechnologyManipalIndia
  9. 9.NIAAA, NIHRockvilleUSA

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