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Molecular Neurobiology

, Volume 41, Issue 2–3, pp 248–255 | Cite as

Targeting Glial Cells to Elucidate the Pathogenesis of Huntington’s Disease

  • Han-Yun Hsiao
  • Yijuang ChernEmail author
Article

Abstract

Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by expended CAG repeats in the Huntingtin (Htt) gene. The resultant mutant Htt (mHtt) forms aggregates in neurons and causes neuronal dysfunctions. The major characteristic of HD is the selective loss of neurons in the striatum and cortex, which leads to movement disorders, dementia, and eventual death. Expression of mHtt was also found in non-neuronal cells in the brain, suggesting non-cell-autonomous neurotoxicity in HD. As was documented in many different neurodegenerative disorders, elevated inflammatory responses are also reported in HD. To date, effective treatments for this devastating disease remain to be developed. This review focuses on the importance of glial cells and inflammation in HD pathogenesis. Potential anti-inflammatory interventions for HD are also discussed.

Keyword

Huntington’s disease Astrocytes Glia Inflammation Neurodegenerative disorder 

Abbreviations

Amyloid β peptide

AD

Alzheimer’s disease

ALS

Amyotrophic lateral sclerosis

BDNF

Brain-derived neurotrophic factor

CNS

Central nervous system

GLT1

Astroglial glutamate transporter

Htt

Huntingtin

HD

Huntington’s disease

mHtt

Mutant Htt

iNOS

Inducible nitric oxide synthase

NO

Nitric oxide

polyQ

Polyglutamine

ROS

Reactive oxygen species

WT

Wildtype

Notes

Acknowledgments

We thank Mr. Dan Chamberlin and Ms. Ihua Hsieh for reading and editing the manuscript, and Mr. Jung-Rung Hung for the artwork. This work was supported by grants (NSC97-2321-B-001-030) from the National Science Council and Academia Sinica, Taipei, Taiwan.

References

  1. 1.
    Neylan TC (2003) Neurodegenerative disorders: George Huntington’s description of hereditary chorea. J Neuropsychiatry Clin Neurosci 15:108PubMedGoogle Scholar
  2. 2.
    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 72:971–983Google Scholar
  3. 3.
    Ryu H, Rosas HD, Hersch SM, Ferrante RJ (2005) The therapeutic role of creatine in Huntington’s disease. Pharmacol Ther 108:193–207PubMedGoogle Scholar
  4. 4.
    Li SH, Li XJ (2004) Huntingtin-protein interactions and the pathogenesis of Huntington’s disease. Trends Genet 20:146–154PubMedGoogle Scholar
  5. 5.
    Sugars KL, Rubinsztein DC (2003) Transcriptional abnormalities in Huntington disease. Trends Genet 19:233–238PubMedGoogle Scholar
  6. 6.
    Wang J, Wang CE, Orr A, Tydlacka S, Li SH, Li XJ (2008) Impaired ubiquitin-proteasome system activity in the synapses of Huntington’s disease mice. J Cell Biol 180:1177–1189PubMedGoogle Scholar
  7. 7.
    Chiang MC, Chen HM, Lai HL, Chen HW, Chou SY, Chen CM, Tsai FJ, Chern Y (2009) The A2A adenosine receptor rescues the urea cycle deficiency of Huntington’s disease by enhancing the activity of the ubiquitin-proteasome system. Hum Mol Genet 18:2929–2942PubMedGoogle Scholar
  8. 8.
    Chiang MC, Chen HM, Lee YH, Chang HH, Wu YC, Soong BW, Chen CM, Wu YR, Liu CS, Niu DM, Wu JY, Chen YT, Chern Y (2007) Dysregulation of C/EBPalpha by mutant Huntingtin causes the urea cycle deficiency in Huntington’s disease. Hum Mol Genet 16:483–498PubMedGoogle Scholar
  9. 9.
    Chiang MC, Lee YC, Huang CL, Chern Y (2005) cAMP-response element-binding protein contributes to suppression of the A2A adenosine receptor promoter by mutant Huntingtin with expanded polyglutamine residues. J Biol Chem 280:14331–14340PubMedGoogle Scholar
  10. 10.
    Chou SY, Lee YC, Chen HM, Chiang MC, Lai HL, Chang HH, Wu YC, Sun CN, Chien CL, Lin YS, Wang SC, Tung YY, Chang C, Chern Y (2005) CGS21680 attenuates symptoms of Huntington’s disease in a transgenic mouse model. J Neurochem 93:310–320PubMedGoogle Scholar
  11. 11.
    Sharp AH, Loev SJ, Schilling G, Li SH, Li XJ, Bao J, Wagster MV, Kotzuk JA, Steiner JP, Lo A et al (1995) Widespread expression of Huntington’s disease gene (IT15) protein product. Neuron 14:1065–1074PubMedGoogle Scholar
  12. 12.
    Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, MacDonald ME, Friedlander RM, Silani V, Hayden MR, Timmusk T, Sipione S, Cattaneo E (2001) Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease. Science 293:493–498PubMedGoogle Scholar
  13. 13.
    Gauthier LR, Charrin BC, Borrell-Pages M, Dompierre JP, Rangone H, Cordelieres 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 118:127–138PubMedGoogle Scholar
  14. 14.
    Gunawardena S, Goldstein LS (2005) Polyglutamine diseases and transport problems: deadly traffic jams on neuronal highways. Arch Neurol 62:46–51PubMedGoogle Scholar
  15. 15.
    Mestre T, Ferreira J, Coelho MM, Rosa M, Sampaio C (2009) Therapeutic interventions for symptomatic treatment in Huntington’s disease. Cochrane Database Syst Rev CD006456Google Scholar
  16. 16.
    Mestre T, Ferreira J, Coelho MM, Rosa M, Sampaio C (2009) Therapeutic interventions for disease progression in Huntington’s disease. Cochrane Database Syst Rev CD006455Google Scholar
  17. 17.
    Reddy PH, Williams M, Tagle DA (1999) Recent advances in understanding the pathogenesis of Huntington’s disease. Trends Neurosci 22:248PubMedGoogle Scholar
  18. 18.
    Waelter S, Boeddrich A, Lurz R, Scherzinger E, Lueder G, Lehrach H, Wanker EE (2001) Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol Biol Cell 12:1393–1407PubMedGoogle Scholar
  19. 19.
    Wang CE, Zhou H, McGuire JR, Cerullo V, Lee B, Li SH, Li XJ (2008) Suppression of neuropil aggregates and neurological symptoms by an intracellular antibody implicates the cytoplasmic toxicity of mutant huntingtin. J Cell Biol 181:803–816PubMedGoogle Scholar
  20. 20.
    Jeong H, Then F, Melia TJ Jr, Mazzulli JR, Cui L, Savas JN, Voisine C, Paganetti P, Tanese N, Hart AC, Yamamoto A, Krainc D (2009) Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell 137:60–72PubMedGoogle Scholar
  21. 21.
    Segovia J, Perez-Severiano F (2004) Oxidative damage in Huntington’s disease. Methods Mol Biol 277:321–334PubMedGoogle Scholar
  22. 22.
    Morton AJ, Leavens W (2000) Mice transgenic for the human Huntington’s disease mutation have reduced sensitivity to kainic acid toxicity. Brain Res Bull 52:51–59PubMedGoogle Scholar
  23. 23.
    Varani K, Rigamonti D, Sipione S, Camurri A, Borea PA, Cattabeni F, Abbracchio MP, Cattaneo E (2001) Aberrant amplification of A(2A) receptor signaling in striatal cells expressing mutant huntingtin. Faseb J 15:1245–1247PubMedGoogle Scholar
  24. 24.
    Martire A, Calamandrei G, Felici F, Scattoni ML, Lastoria G, Domenici MR, Tebano MT, Popoli P (2007) Opposite effects of the A2A receptor agonist CGS21680 in the striatum of Huntington’s disease versus wild-type mice. Neurosci Lett 417:78–83PubMedGoogle Scholar
  25. 25.
    Li X, Sapp E, Chase K, Comer-Tierney LA, Masso N, Alexander J, Reeves P, Kegel KB, Valencia A, Esteves M, Aronin N, Difiglia M (2009) Disruption of Rab11 activity in a knock-in mouse model of Huntington’s disease. Neurobiol Dis 36:374–383PubMedGoogle Scholar
  26. 26.
    Cha JH, Kosinski CM, Kerner JA, Alsdorf SA, Mangiarini L, Davies SW, Penney JB, Bates GP, Young AB (1998) Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci U S A 95:6480–6485PubMedGoogle Scholar
  27. 27.
    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 86:2667–2677PubMedGoogle Scholar
  28. 28.
    Cepeda C, Wu N, Andre VM, Cummings DM, Levine MS (2007) The corticostriatal pathway in Huntington’s disease. Prog Neurobiol 81:253–271PubMedGoogle Scholar
  29. 29.
    Zhang H, Li Q, Graham RK, Slow E, Hayden MR, Bezprozvanny I (2008) Full length mutant huntingtin is required for altered Ca2+ signaling and apoptosis of striatal neurons in the YAC mouse model of Huntington’s disease. Neurobiol Dis 31:80–88PubMedGoogle Scholar
  30. 30.
    Liu J, Tang TS, Tu H, Nelson O, Herndon E, Huynh DP, Pulst SM, Bezprozvanny I (2009) Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 2. J Neurosci 29:9148–9162PubMedGoogle Scholar
  31. 31.
    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 171:1001–1012PubMedGoogle Scholar
  32. 32.
    Chou SY, Weng JY, Lai HL, Liao F, Sun SH, Tu PH, Dickson DW, Chern Y (2008) Expanded-polyglutamine huntingtin protein suppresses the secretion and production of a chemokine (CCL5/RANTES) by astrocytes. J Neurosci 28:3277–3290PubMedGoogle Scholar
  33. 33.
    Bjorkqvist M, Wild EJ, Thiele J, Silvestroni A, Andre R, Lahiri N, Raibon E, Lee RV, Benn CL, Soulet D, Magnusson A, Woodman B, Landles C, Pouladi MA, Hayden MR, Khalili-Shirazi A, Lowdell MW, Brundin P, Bates GP, Leavitt BR, Moller T, Tabrizi SJ (2008) A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington’s disease. J Exp Med 205:1869–1877PubMedGoogle Scholar
  34. 34.
    Singhrao SK, Neal JW, Morgan BP, Gasque P (1999) Increased complement biosynthesis by microglia and complement activation on neurons in Huntington’s disease. Exp Neurol 159:362–376PubMedGoogle Scholar
  35. 35.
    Roos RA, Bots GT, Hermans J (1985) Neuronal nuclear membrane indentation and astrocyte/neuron ratio in Huntington’s disease. A quantitative electron microscopic study. J Hirnforsch 26:689–693PubMedGoogle Scholar
  36. 36.
    Simmons DA, Casale M, Alcon B, Pham N, Narayan N, Lynch G (2007) Ferritin accumulation in dystrophic microglia is an early event in the development of Huntington’s disease. Glia 55:1074–1084PubMedGoogle Scholar
  37. 37.
    Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, Piccini P (2007) Microglial activation in presymptomatic Huntington’s disease gene carriers. Brain 130:1759–1766PubMedGoogle Scholar
  38. 38.
    Lin CH, Tallaksen-Greene S, Chien WM, Cearley JA, Jackson WS, Crouse AB, Ren S, Li XJ, Albin RL, Detloff PJ (2001) Neurological abnormalities in a knock-in mouse model of Huntington’s disease. Hum Mol Genet 10:137–144PubMedGoogle Scholar
  39. 39.
    Rodriguez JJ, Olabarria M, Chvatal A, Verkhratsky A (2009) Astroglia in dementia and Alzheimer’s disease. Cell Death Differ 16:378–385PubMedGoogle Scholar
  40. 40.
    Volterra A, Meldolesi J (2005) Astrocytes, from brain glue to communication elements: the revolution continues. Nat Rev Neurosci 6:626PubMedGoogle Scholar
  41. 41.
    Maragakis NJ, Rothstein JD (2006) Mechanisms of disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol 2:679–689PubMedGoogle Scholar
  42. 42.
    Ridet JL, Malhotra SK, Privat A, Gage FH (1997) Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 20:570–577PubMedGoogle Scholar
  43. 43.
    Vila M, Jackson-Lewis V, Guegan C, Wu DC, Teismann P, Choi DK, Tieu K, Przedborski S (2001) The role of glial cells in Parkinson’s disease. Curr Opin Neurol 14:483–489PubMedGoogle Scholar
  44. 44.
    Maragakis NJ, Rothstein JD (2004) Glutamate transporters: animal models to neurologic disease. Neurobiol Dis 15:461–473PubMedGoogle Scholar
  45. 45.
    Clement AM, Nguyen MD, Roberts EA, Garcia ML, Boillee S, Rule M, McMahon AP, Doucette W, Siwek D, Ferrante RJ, Brown RH Jr, Julien JP, Goldstein LS, Cleveland DW (2003) Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 302:113–117PubMedGoogle Scholar
  46. 46.
    Forman MS, Lal D, Zhang B, Dabir DV, Swanson E, Lee VM, Trojanowski JQ (2005) Transgenic mouse model of tau pathology in astrocytes leading to nervous system degeneration. J Neurosci 25:3539–3550PubMedGoogle Scholar
  47. 47.
    Bristol LA, Rothstein JD (1996) Glutamate transporter gene expression in amyotrophic lateral sclerosis motor cortex. Ann Neurol 39:676–679PubMedGoogle Scholar
  48. 48.
    Barbeito LH, Pehar M, Cassina P, Vargas MR, Peluffo H, Viera L, Estevez AG, Beckman JS (2004) A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis. Brain Res Brain Res Rev 47:263–274PubMedGoogle Scholar
  49. 49.
    Lievens 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 8:807–821PubMedGoogle Scholar
  50. 50.
    Bradford J, Shin JY, Roberts M, Wang CE, Li X-J, Li S (2010) Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc Natl Acad Sci U S A, Epub Ahead of PrintGoogle Scholar
  51. 51.
    Fowler SC, Miller BR, Gaither TW, Johnson MA, Rebec GV (2009) Force-plate quantification of progressive behavioral deficits in the R6/2 mouse model of Huntington’s disease. Behav Brain Res 202:130–137PubMedGoogle Scholar
  52. 52.
    Heales SJ, Lam AA, Duncan AJ, Land JM (2004) Neurodegeneration or neuroprotection: the pivotal role of astrocytes. Neurochem Res 29:513–519PubMedGoogle Scholar
  53. 53.
    Chen PS, Peng GS, Li G, Yang S, Wu X, Wang CC, Wilson B, Lu RB, Gean PW, Chuang DM, Hong JS (2006) Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes. Mol Psychiatry 11:1116–1125PubMedGoogle Scholar
  54. 54.
    Saavedra A, Baltazar G, Santos P, Carvalho CM, Duarte EP (2006) Selective injury to dopaminergic neurons up-regulates GDNF in substantia nigra postnatal cell cultures: role of neuron-glia crosstalk. Neurobiol Dis 23:533–542PubMedGoogle Scholar
  55. 55.
    Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F (1993) GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260:1130–1132PubMedGoogle Scholar
  56. 56.
    Appay V, Rowland-Jones SL (2001) RANTES: a versatile and controversial chemokine. Trends in Immunology 22:83PubMedGoogle Scholar
  57. 57.
    Bolin LM, Murray R, Lukacs NW, Strieter RM, Kunkel SL, Schall TJ, Bacon KB (1998) Primary sensory neurons migrate in response to the chemokine RANTES. J Neuroimmunol 81:49–57PubMedGoogle Scholar
  58. 58.
    Bakhiet M, Tjernlund A, Mousa A, Gad A, Stromblad S, Kuziel WA, Seiger A, Andersson J (2001) RANTES promotes growth and survival of human first-trimester forebrain astrocytes. Nat Cell Biol 3:150–157PubMedGoogle Scholar
  59. 59.
    Spires TL, Grote HE, Garry S, Cordery PM, Van Dellen A, Blakemore C, Hannan AJ (2004) Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington’s disease transgenic mice. Eur J NeuroSci 19:2799–2807PubMedGoogle Scholar
  60. 60.
    Ariano MA, Cepeda C, Calvert CR, Flores-Hernandez J, Hernandez-Echeagaray E, Klapstein GJ, Chandler SH, Aronin N, DiFiglia M, Levine MS (2005) Striatal potassium channel dysfunction in Huntington’s disease transgenic mice. J Neurophysiol 93:2565–2574PubMedGoogle Scholar
  61. 61.
    El Khoury J, Luster AD (2008) Mechanisms of microglia accumulation in Alzheimer’s disease: therapeutic implications. Trends Pharmacol Sci 29:626–632PubMedGoogle Scholar
  62. 62.
    Klegeris A, McGeer EG, McGeer PL (2007) Therapeutic approaches to inflammation in neurodegenerative disease. Curr Opin Neurol 20:351–357PubMedGoogle Scholar
  63. 63.
    Sargsyan SA, Monk PN, Shaw PJ (2005) Microglia as potential contributors to motor neuron injury in amyotrophic lateral sclerosis. Glia 51:241–253PubMedGoogle Scholar
  64. 64.
    Hansson E, Ronnback L (2003) Glial neuronal signaling in the central nervous system. Faseb J 17:341–348PubMedGoogle Scholar
  65. 65.
    Lai AY, Todd KG (2006) Microglia in cerebral ischemia: molecular actions and interactions. Can J Physiol Pharmacol 84:49–59PubMedGoogle Scholar
  66. 66.
    Ii M, Sunamoto M, Ohnishi K, Ichimori Y (1996) Beta-amyloid protein-dependent nitric oxide production from microglial cells and neurotoxicity. Brain Res 720:93–100PubMedGoogle Scholar
  67. 67.
    Roy A, Jana A, Yatish K, Freidt MB, Fung YK, Martinson JA, Pahan K (2008) Reactive oxygen species up-regulate CD11b in microglia via nitric oxide: implications for neurodegenerative diseases. Free Radic Biol Med 45:686–699PubMedGoogle Scholar
  68. 68.
    Jiao J, Xue B, Zhang L, Gong Y, Li K, Wang H, Jing L, Xie J, Wang X (2008) Triptolide inhibits amyloid-beta1-42-induced TNF-alpha and IL-1beta production in cultured rat microglia. J Neuroimmunol 205:32–36PubMedGoogle Scholar
  69. 69.
    Szaingurten-Solodkin I, Hadad N, Levy R (2009) Regulatory role of cytosolic phospholipase A2alpha in NADPH oxidase activity and in inducible nitric oxide synthase induction by aggregated Abeta1-42 in microglia. Glia 57:1727–1740PubMedGoogle Scholar
  70. 70.
    Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O’Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421PubMedGoogle Scholar
  71. 71.
    McGeer PL, McGeer EG (1999) Inflammation of the brain in Alzheimer’s disease: implications for therapy. J Leukoc Biol 65:409–415PubMedGoogle Scholar
  72. 72.
    Wyss-Coray T, Yan F, Lin AH, Lambris JD, Alexander JJ, Quigg RJ, Masliah E (2002) Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer’s mice. Proc Natl Acad Sci U S A 99:10837–10842PubMedGoogle Scholar
  73. 73.
    Rotshenker S (2003) Microglia and macrophage activation and the regulation of complement-receptor-3 (CR3/MAC-1)-mediated myelin phagocytosis in injury and disease. J Mol Neurosci 21:65–72PubMedGoogle Scholar
  74. 74.
    Hald A, Lotharius J (2005) Oxidative stress and inflammation in Parkinson’s disease: is there a causal link? Exp Neurol 193:279–290PubMedGoogle Scholar
  75. 75.
    Wu DC, Teismann P, Tieu K, Vila M, Jackson-Lewis V, Ischiropoulos H, Przedborski S (2003) NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine model of Parkinson’s disease. Proc Natl Acad Sci U S A 100:6145–6150PubMedGoogle Scholar
  76. 76.
    Jana S, Maiti AK, Bagh MB, Banerjee K, Das A, Roy A, Chakrabarti S (2007) Dopamine but not 3, 4-dihydroxy phenylacetic acid (DOPAC) inhibits brain respiratory chain activity by autoxidation and mitochondria catalyzed oxidation to quinone products: implications in Parkinson’s disease. Brain Res 1139:195–200PubMedGoogle Scholar
  77. 77.
    Orth M, Schapira AH (2002) Mitochondrial involvement in Parkinson’s disease. Neurochem Int 40:533–541PubMedGoogle Scholar
  78. 78.
    Tabrizi SJ, Workman J, Hart PE, Mangiarini L, Mahal A, Bates G, Cooper JM, Schapira AH (2000) Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Ann Neurol 47:80–86PubMedGoogle Scholar
  79. 79.
    Pavese N, Gerhard A, Tai YF, Ho AK, Turkheimer F, Barker RA, Brooks DJ, Piccini P (2006) Microglial activation correlates with severity in Huntington disease: a clinical and PET study. Neurology 66:1638–1643PubMedGoogle Scholar
  80. 80.
    Mennicken F, Maki R, de Souza EB, Quirion R (1999) Chemokines and chemokine receptors in the CNS: a possible role in neuroinflammation and patterning. Trends Pharmacol Sci 20:73–78PubMedGoogle Scholar
  81. 81.
    Nguyen MD, Julien JP, Rivest S (2002) Innate immunity: the missing link in neuroprotection and neurodegeneration? Nat Rev Neurosci 3:216–227PubMedGoogle Scholar
  82. 82.
    Rogers J, Mastroeni D, Leonard B, Joyce J, Grover A (2007) Neuroinflammation in Alzheimer’s disease and Parkinson’s disease: are microglia pathogenic in either disorder? Int Rev Neurobiol 82:235–246PubMedGoogle Scholar
  83. 83.
    Boillee S, Vande Velde C, Cleveland DW (2006) ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron 52:39–59PubMedGoogle Scholar
  84. 84.
    McGeer PL, McGeer EG (2008) Glial reactions in Parkinson’s disease. Mov Disord 23:474–483PubMedGoogle Scholar
  85. 85.
    Sastre M, Klockgether T, Heneka MT (2006) Contribution of inflammatory processes to Alzheimer’s disease: molecular mechanisms. Int J Dev Neurosci 24:167–176PubMedGoogle Scholar
  86. 86.
    Calabrese V, Boyd-Kimball D, Scapagnini G, Butterfield DA (2004) Nitric oxide and cellular stress response in brain aging and neurodegenerative disorders: the role of vitagenes. In Vivo 18:245–267PubMedGoogle Scholar
  87. 87.
    Deckel AW (2001) Nitric oxide and nitric oxide synthase in Huntington’s disease. J Neurosci Res 64:99–107PubMedGoogle Scholar
  88. 88.
    Blanco AM, Guerri C (2007) Ethanol intake enhances inflammatory mediators in brain: role of glial cells and TLR4/IL-1RI receptors. Front Biosci 12:2616–2630PubMedGoogle Scholar
  89. 89.
    Marchetti B, Serra PA, Tirolo C, L’Episcopo F, Caniglia S, Gennuso F, Testa N, Miele E, Desole S, Barden N, Morale MC (2005) Glucocorticoid receptor-nitric oxide crosstalk and vulnerability to experimental parkinsonism: pivotal role for glia-neuron interactions. Brain Res Brain Res Rev 48:302–321PubMedGoogle Scholar
  90. 90.
    Beattie MS (2004) Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med 10:580–583PubMedGoogle Scholar
  91. 91.
    Heneka MT, Sastre M, Dumitrescu-Ozimek L, Hanke A, Dewachter I, Kuiperi C, O’Banion K, Klockgether T, Van Leuven F, Landreth GE (2005) Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. Brain 128:1442–1453PubMedGoogle Scholar
  92. 92.
    Jantzen PT, Connor KE, DiCarlo G, Wenk GL, Wallace JL, Rojiani AM, Coppola D, Morgan D, Gordon MN (2002) Microglial activation and beta -amyloid deposit reduction caused by a nitric oxide-releasing nonsteroidal anti-inflammatory drug in amyloid precursor protein plus presenilin-1 transgenic mice. J Neurosci 22:2246–2254PubMedGoogle Scholar
  93. 93.
    McGeer PL, Rogers J, McGeer EG (2006) Inflammation, anti-inflammatory agents and Alzheimer disease: the last 12 years. J Alzheimers Dis 9:271–276PubMedGoogle Scholar
  94. 94.
    Seabrook TJ, Jiang L, Maier M, Lemere CA (2006) Minocycline affects microglia activation, Abeta deposition, and behavior in APP-tg mice. Glia 53:776–782PubMedGoogle Scholar
  95. 95.
    Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57–69PubMedGoogle Scholar
  96. 96.
    McGeer PL, Yasojima K, McGeer EG (2001) Inflammation in Parkinson’s disease. Adv Neurol 86:83–89PubMedGoogle Scholar
  97. 97.
    Langston JW, Forno LS, Tetrud J, Reeves AG, Kaplan JA, Karluk D (1999) Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine exposure. Ann Neurol 46:598–605PubMedGoogle Scholar
  98. 98.
    Wyss-Coray T, Mucke L (2002) Inflammation in neurodegenerative disease–a double-edged sword. Neuron 35:419–432PubMedGoogle Scholar
  99. 99.
    Liu B, Hong JS (2003) Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther 304:1–7PubMedGoogle Scholar
  100. 100.
    Purisai MG, McCormack AL, Cumine S, Li J, Isla MZ, Di Monte DA (2007) Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration. Neurobiol Dis 25:392–400PubMedGoogle Scholar
  101. 101.
    Glezer I, Simard AR, Rivest S (2007) Neuroprotective role of the innate immune system by microglia. Neuroscience 147:867–883PubMedGoogle Scholar
  102. 102.
    Simard AR, Soulet D, Gowing G, Julien JP, Rivest S (2006) Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 49:489–502PubMedGoogle Scholar
  103. 103.
    Monsonego A, Weiner HL (2003) Immunotherapeutic approaches to Alzheimer’s disease. Science 302:834–838PubMedGoogle Scholar
  104. 104.
    Wang X, Zhu S, Drozda M, Zhang W, Stavrovskaya IG, Cattaneo E, Ferrante RJ, Kristal BS, Friedlander RM (2003) Minocycline inhibits caspase-independent and -dependent mitochondrial cell death pathways in models of Huntington’s disease. Proc Natl Acad Sci U S A 100:10483–10487PubMedGoogle Scholar
  105. 105.
    Stack EC, Smith KM, Ryu H, Cormier K, Chen M, Hagerty SW, Del Signore SJ, Cudkowicz ME, Friedlander RM, Ferrante RJ (2006) Combination therapy using minocycline and coenzyme Q10 in R6/2 transgenic Huntington’s disease mice. Biochim Biophys Acta 1762:373–380PubMedGoogle Scholar
  106. 106.
    Mievis S, Levivier M, Communi D, Vassart G, Brotchi J, Ledent C, Blum D (2007) Lack of minocycline efficiency in genetic models of Huntington’s disease. Neuromolecular Med 9:47–54PubMedGoogle Scholar
  107. 107.
    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 87:493–506PubMedGoogle Scholar
  108. 108.
    Giorgini F, Moller T, Kwan W, Zwilling D, Wacker JL, Hong S, Tsai LC, Cheah CS, Schwarcz R, Guidetti P, Muchowski PJ (2008) Histone deacetylase inhibition modulates kynurenine pathway activation in yeast, microglia, and mice expressing a mutant huntingtin fragment. J Biol Chem 283:7390–7400PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Division of NeuroscienceInstitute of Biomedical Sciences, Academia SinicaTaipeiTaiwan
  2. 2.Institute of NeuroscienceNational Yang Ming UniversityTaipeiTaiwan

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