Neurodegenerative Disease Conditions and Genomic Treatment for Better Health

  • Ravindra V. Badhe
  • Dharmesh R. Chejara
  • Pradeep Kumar
  • Yahya E. Choonara
  • Viness PillayEmail author


Neurodegenerative diseases are genetic and/or sporadic disease conditions characterized by progressive nervous system dysfunction involving the atrophy of central or peripheral nervous. The neurodegenerative diseases (NDs) like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) are responsible for more than 1% deaths and more than 2% disabilities of total world population. These NDs also impart huge socioeconomical burden on families of patients. NDs involve complex etiology with different genetic and environmental factors. The understanding of the etiology may help therapists to develop new effective symptomatic and preventive (genetic) treatments for NDs. The development in Human Genome Project helping to detect the genetic mutations causing HDs and advancement in gene and genome therapy are being implemented to correct these mutations. In this chapter, Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) are discussed in detail for their pathophysiology, etiology, and latest symptomatic and preventive treatment. In preventive treatment, the latest achievements of the gene and genomic therapies are discussed.


Alzheimer’s disease Parkinson’s disease Huntington’s disease Amyotrophic lateral sclerosis Genomic treatment 


  1. 1.
    Bredesen DE, Rao RV, Mehlen P (2006) Cell death in the nervous system. Nature 443(7113):796–802PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Thompson LM (2008) Neurodegeneration: a question of balance. Nature 452(7188):707–708PubMedCrossRefGoogle Scholar
  3. 3.
    Rubinsztein DC (2008) The roles of intracellular protein-degradation pathways in neurodegeneration. Nature 443(7113):780–786CrossRefGoogle Scholar
  4. 4.
    Marsh JL, Lukacsovich T, Thompson LM (2009) Animal models of Polyglutamine diseases and therapeutic approaches. J Biol Chem 284(12):7431–7435PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Zoghbi HY, Orr HT (2009) Pathogenic mechanisms of a Polyglutamine-mediated neurodegenerative disease, Spinocerebellar ataxia type 1. J Biol Chem 284(12):7425–7429PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Coleman MP, Freeman MF (2010) Wallerian degeneration, WldS and Nmnat. Ann Rev Neurosci 33:245–267PubMedCrossRefGoogle Scholar
  7. 7.
    De Vos KJ, Grierson AJ, Ackerley S, Miller CC (2008) Role of axonal transport in neurodegenerative diseases. Ann Rev Neurosci 31:151–173PubMedCrossRefGoogle Scholar
  8. 8.
    DiMauro S, Schon EA (2008) Mitochondrial disorders in the nervous system. Ann Rev Neurosci 31:91–123PubMedCrossRefGoogle Scholar
  9. 9.
    Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443(7113):787–795PubMedCrossRefGoogle Scholar
  10. 10.
    Martindale JL, Holbrook NJ (2002) Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol 192(1):1–15PubMedCrossRefGoogle Scholar
  11. 11.
    Tafani M, Karpinich NO, Hurster KA, Pastorino JG, Schneider T, Russo MA, Farber JL (2002) Cytochrome C release upon Fas receptor activation depends on translocation of full-length bid and the induction of the mitochondrial permeability transition. J Biol Chem 277(12):10073–10082PubMedCrossRefGoogle Scholar
  12. 12.
    Engelberg-Kulka H, Amitai S, Kolodkin-Gal I, Hazan R (2006) Bacterial programmed cell death and multicellular behavior in bacteria. PLoS Genet 2(10):e135PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Kimichi A, Kroemer G, Zalckvar E, Chiara MM (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8:741–752Google Scholar
  14. 14.
    Vila M, Przedbroski S (2003) Targeting programmed cell death in neurodegenerative diseases. Nat Rev Neurosci 4:1–11CrossRefGoogle Scholar
  15. 15.
    Neurological disorders: public health challenges (2006) Report by World Health Organization, Geneva, Switzerland.
  16. 16.
    Alzheimer’s association (2015) Alzheimer’s disease facts and figures. Alzheimer’s Dementia 11(3):332–384CrossRefGoogle Scholar
  17. 17.
    Huse DM, Schulman K, Orsini L, Castelli-Haley J, Kennedy S, Lenhart G (2005) Burden of illness in Parkinson’s disease. Mov Disord 20(11):1449–1454PubMedCrossRefGoogle Scholar
  18. 18.
    Kandale VV, Mujawar SN, Welasly PJ, Nimbalkar JM (2013) Development of integrated database of neurodegenerative diseases (IDND). Rev Res 2(9):1–5Google Scholar
  19. 19.
    Kowal SL, Dall TM, Chakrabarti R, Storm MV, Jain A (2013) The current and projected economic burden of Parkinson’s disease in the United States. Mov Disord 28(3):311–318PubMedCrossRefGoogle Scholar
  20. 20.
    Mathers CD, Loncar D (2005) Updated projections of global mortality and burden of disease, 2002–2030: data sources, methods and results. World Health Organization, Geneva. (Evidence and Information for Policy Working Paper). Google Scholar
  21. 21.
    Mathers CD, Salomon JA, Ezzati M, Begg S, Lopez AD (2006) Sensitivity and uncertainty analyses for burden of disease and risk factor estimates. In: Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJL (eds) Global burden of disease and risk factors. The World Bank, Oxford University Press, Washington, pp 399–426Google Scholar
  22. 22.
    Murray CJL, Lopez AD (1997) Alternative projections of mortality and disability by cause, 1990–2020: global burden of disease study. Lancet 349:1498–1504PubMedCrossRefGoogle Scholar
  23. 23.
    The world health report (2004) Changing history. World Health Organization, GenevaGoogle Scholar
  24. 24.
    Azzouz M, Kingsman SM, Mazarakis ND (2004) Lentiviral vectors for treating and modeling human CNS disorders. J Gene Med 6(9):951–962PubMedCrossRefGoogle Scholar
  25. 25.
    Nanou A, Azzouz M (2009) Gene therapy for neurodegenerative diseases based on lentiviral vectors. Prog Brain Res 175:187–200PubMedCrossRefGoogle Scholar
  26. 26.
    Wong LF, Goodhead L, Prat C, Mitrophanous KA, Kingsman SM, Mazarakis ND (2006) Lentivirus-mediated gene transfer to the central nervous system: therapeutic and research applications. Hum Gene Ther 17(1):1–9PubMedCrossRefGoogle Scholar
  27. 27.
    Geller G, Dvoskin R, Thio CL, Duggal P, Lewis MH, Bailey TC, Sutherland A, Salmon DA, Kahn JP (2014) Genomics and infectious disease: a call to identify the ethical, legal and social implications for public health and clinical practice. Genome Med 6(11):106–118PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10):883–892PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Tuteja S, Rader DJ (2012) Genomic medicine in the prevention and treatment of atherosclerotic cardiovascular disease. Pers Med 9(4):395–404CrossRefGoogle Scholar
  30. 30.
    Karr JR, Sanghvi JC, Macklin DN, Gutschow MV, Jacobs JM, Bolival B Jr et al (2012) A whole-cell computational model predicts phenotype from genotype. Cell 150(2):389–401PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Dancey JE, Bedard PL, Onetto N, Hudson TJ (2012) The genetic basis for cancer treatment decisions. Cell 148(3):409–420PubMedCrossRefGoogle Scholar
  32. 32.
    National Institute of Neurological Disorders and Stroke. Dementia: hope through research. Bethesda, MD (2013) Office of Communications and Public Liaison, National Institute of Neurological Disorders and Stroke, US National Institutes of Health. Published online; version last updated June 26th, 2013, accessed November 1st, 2013Google Scholar
  33. 33.
    Alzheimer’s Association (2013) The role of plaques and tangles. Published online, accessed Accessed 01 Nov 2013
  34. 34.
    Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT (2011) Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Biol 3(9):a006189Google Scholar
  35. 35.
    Davinelli S, Intrieri M, Russo C, Di Costanzo A, Zella D, Bosco P, Giovanni S (2011) The “Alzheimer’s disease signature”: potential perspectives for novel biomarkers. Immune Ageing 20(8):7–17CrossRefGoogle Scholar
  36. 36.
    Goldman JS, Hahn SE, Catania JW, LaRusse-Eckert S, Butson MB, Rumbaugh M, Strecker MN, Roberts JS, Burke W, Mayeux R, Bird T (2011) Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of genetic Counselors. Genet Med 13(6):597–605PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Baker LD, Cross DJ, Minoshima S, Belongia D, Watson GS, Craft S (2011) Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. Arch Neurol 68(1):51–57PubMedCrossRefGoogle Scholar
  38. 38.
    Miklossy J (2011) Emerging roles of pathogens in Alzheimer disease. Expert Rev Mol Med 13:e30PubMedCrossRefGoogle Scholar
  39. 39.
    Magnoni S, Brody DL (2010) New perspectives on amyloid-beta dynamics after acute brain injury: moving between experimental approaches and studies in the human brain. Arch Neurol 67(9):1068–1073PubMedCrossRefGoogle Scholar
  40. 40.
    Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, al e (2007) Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 6:734–746PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Ballard CG, Gauthier S, Cummings JL, Brodaty H, Grossberg GT, Robert P, Lyketsos CG (2009) Management of agitation and aggression associated with Alzheimer disease. Nat Rev Neurol 5:245–255PubMedCrossRefGoogle Scholar
  42. 42.
    Savva GM, Zaccai J, Matthews FE, Davidson JE, McKeith I, Brayne C (2009) Medical Research Council cognitive function and ageing study. Prevalence correlates and course of behavioural and psychological symptoms of dementia in the population. Br J Psychiatry 194:212–219PubMedCrossRefGoogle Scholar
  43. 43.
    Galimberti G, Scarpini E (2013) Treatment of Alzheimer’s disease: symptomatic and disease-modifying approaches. Curr Aging Sci 3(1):46–56CrossRefGoogle Scholar
  44. 44.
    Prevention and Risk of Alzheimer’s and Dementia (2015) Alzheimer’s Association, Chicago, IL, USA.
  45. 45.
    Nagahara AH, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shaked GM, Wang L, Blesch A, Kim A, Conner JM, Rockenstein E, Chao MV, Koo EH, Geschwind D, Masliah E, Chiba AA, Tuszynski MH (2009) Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease. Nat Med 15:331–337PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Annunziata I, Patterson A, Helton D, Hu H, Moshiach S, Gomero E, Nixon R, d’Azzo R, Lysosomal NEU (2013) Deficiency affects amyloid precursor protein levels and amyloid-β secretion via deregulated lysosomal exocytosis. Nat Commun 4:2734PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Minami SS, Min SM, Krabbe G, Wang C, Zhou Y, Asgarov R, Li Y, Martens LH, Elia LP, Ward ME, Mucke L, Farese Jr RV, Gan L (2014) Progranulin protects against amyloid β deposition and toxicity in Alzheimer’s disease mouse models. Nat Med 20:1157–1164PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Parra-Damas A, Valero J, Chen M, España J, Martin E, Ferrer I, Rodríguez-Alvarez J, Saura CA (2014) Crtc1 activates a transcriptional program deregulated at early Alzheimer's disease-related stages. J Neurosci 34(17):5776–5787PubMedCrossRefGoogle Scholar
  49. 49.
    Chinta S, Lieu C, Demaria M, Laberge R, Campisi J, Anderson J (2013) Environmental stress, ageing, and glial cell senescence: a novel mechanistic link to Parkinson’s disease. J Internal Med 273:429–436PubMedCrossRefGoogle Scholar
  50. 50.
    Chou K (2013) Clinical manifestations of Parkinson Disease. Up-to-date. Accessed 22 July 2013
  51. 51.
    Fritsch T, Smyth K, Wallendal M, Hyde T, Leo G, Geldmacher D (2012) Parkinson disease: research update and clinical management. South Med J 105(12):650–656PubMedCrossRefGoogle Scholar
  52. 52.
    Gazewood J, Richards D, Clebak K (2013) Parkinson disease: an update. Am Family Phys 87(4):267–273Google Scholar
  53. 53.
    MacPhee G, Stewart D (2001) Parkinson’s disease. Rev Clin Gerontol 11:33–49CrossRefGoogle Scholar
  54. 54.
    Parkinson’s Disease Foundation: Statistics on Parkinson’s (2013) Retrieved on 22 July 2013 from
  55. 55.
    Sherer TB, Chowdhury S, Peabody K, Brooks DW (2012) Overcoming obstacles in Parkinson's disease. Mov Disord 27(13):1606–1611PubMedCrossRefGoogle Scholar
  56. 56.
    Jankovic J, Hurtig H, Dashe J (2013) Etiology and pathogenesis of Parkinson Disease. Up-to-date. Accessed 22 July 2013
  57. 57.
    Postuma R, Gagnon J, Montplaisir J (2009) Clinical prediction of Parkinson’s disease: planning for the age of neuroprotection. J Neurol 81(9):1008–1013Google Scholar
  58. 58.
    Duda JE, Lee VM, Trojanowski JQ (2000) Neuropathology of synuclein aggregates. J Neurosci Res 61(2):121–127PubMedCrossRefGoogle Scholar
  59. 59.
    Bendor JT, Logan TP, Edwards RH (2013) The function of α-Synuclein. Neuron 79(6):1044–1066PubMedCrossRefGoogle Scholar
  60. 60.
    Beitz JM (2014) Parkinson’s disease: a review. Front Biosci S6:65–74CrossRefGoogle Scholar
  61. 61.
    Hawkes C, Del K, Braak TH (2007) Review: Parkinson's disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol 33:599–614PubMedCrossRefGoogle Scholar
  62. 62.
    Brown T, Rumsby P, Capleton A, Rushton L, Levy L (2006) Pesticides and Parkinson's disease: is there a link? Environ Health Persp 14(2):156–164CrossRefGoogle Scholar
  63. 63.
    Ceccatelli S (2013) Mechanisms of neurotoxicity and implications for neurological disorders. J Internal Med 273:426–429PubMedCrossRefGoogle Scholar
  64. 64.
    Connolly BS, Lang AE (2014) Pharmacological treatment of Parkinson disease - a review. JAMA 311(16):1670–1683PubMedCrossRefGoogle Scholar
  65. 65.
    Olanow CW (2004) The scientific basis for the current treatment of parkinson’s disease. Annu Rev Med 55:41–60PubMedCrossRefGoogle Scholar
  66. 66.
    Kim C, Han B, Moon J, Kim D, Shin J, Rajan S, Nguyen QT, Sohn M, Kim W, Han M et al (2015) Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson’s disease. PNAS 112(28):8756–8761PubMedCrossRefGoogle Scholar
  67. 67.
    Zharikov AD, Cannon JR, Tapias V, Bai Q, Horowitz MP, Shah V, Ayadi AE, Hastings TG, Greenamyre JT, Burton EA (2015) shRNA targeting α-synuclein prevents neurodegeneration in a Parkinson’s disease model. J Clin Investig 125(7):2721–2735PubMedCrossRefGoogle Scholar
  68. 68.
    Palfi S, Gurruchaga JM, Ralph GS, Lepetit H, Lavisse S, Buttery PC, Watts C, Miskin J, Kelleher M, Deeley S et al (2014) Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial. Lancet 383(9923):1138–1146PubMedCrossRefGoogle Scholar
  69. 69.
    Huntington G (1872) On chorea. Med Surg Report 26:320–321Google Scholar
  70. 70.
    Parikshak NN, Gandal MJ, Geschwind DH (2015) Systems biology and gene networks in neurodevelopmental and neurodegenerative disorders. Nat Rev Genetics 16:441–458PubMedCrossRefGoogle Scholar
  71. 71.
    Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA (2007) The worldwide prevalence of ADHD: a systematic review and Metaregression analysis. Am J Psychiatry 164(6):942–948PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Schneider SA, Bhatia KP (2012) In: Weiner WJ, Tolosa E (eds) Chapter 5 – Huntington’s disease look-alikes in handbook of clinical neurology (hyperkinetic movement disorders), vol 100 (3rd. series). Elsevier, Amsterdam, pp 101–111Google Scholar
  73. 73.
    Paulson HL, Albin RL (2011a) In: Lo DC, Hughes RE (eds) Chapter 1 Huntington’s disease - clinical features and routes to therapy in neurobiology of Huntington's disease: applications to drug discovery. CRC Press, Boca Raton, pp 1–38Google Scholar
  74. 74.
    Shirasaki DI, Greiner ER, Al-Ramahi I, Gray M, Boontheung P, Geschwind DH, Botas J, Coppola G, Horvath S, Loo JA, Yang XW (2012) Network organization of the Huntington proteomic interactome in mammalian brain. Neuron 75:41–57PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackell E, Marder K, Penchaszadeh G, Roberts SA, Gayán J et al (2004) Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington’s disease age of onset. PNAS 101(10):3498–3503PubMedCrossRefGoogle Scholar
  76. 76.
    Wexler NS, Young AB, Tanzi RE, Travers H, Starosta-Rubinstein S, Penney JB, Snodgrass SR, Shoulson I, Gomez F, Ramos Arroyo MA et al (1987) Homozygotes for Huntington's disease. Nature 326(6109):194–197PubMedCrossRefGoogle Scholar
  77. 77.
    Cleret de Langavant L, Fénelon G, Benisty S, Boissé MF, Jacquemot C, AC BL (2013) Awareness of memory deficits in early stage Huntington's disease. PLoS One 8(4):e61676PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Ho A, Hocaoglu M (2011) Impact of Huntington's across the entire disease spectrum: the phases and stages of disease from the patient perspective. Clin Genet 80(3):235–239PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Loy CT, McCusker EA (2013) Is a motor criterion essential for the diagnosis of clinical huntington disease? PLoS Curr 5. ecurrents.hd.f4c66bd51e8db11f55e1701af937a419. doi:
  80. 80.
    Nucifora FC Jr, Sasaki M, Peters MF, Huang H, Cooper JK, Yamada M, Taka- hashi H, Tsuji S, Troncoso J, Dawson VL et al (2001) Interference by Huntington and atrophin1 with cbpmediated transcription leading to cellular toxicity. Science 291(5512):2423–2428PubMedCrossRefGoogle Scholar
  81. 81.
    Revilla FJ, Grutzendler J, Larsh TR (2015) Huntington disease- background, pathophysiology, Etiology. In: Benbadis SR, Talavera F (eds) Medscape reference - drugs, diseases and procedures. Article 1150165Google Scholar
  82. 82.
    Beister A, Kraus P, Kuhn W, Dose M, Weindl A, Gerlach M (2004) The NmethylD aspartate antagonist Memantine retards progression of Huntington’s disease. J Neural Transm Suppl 68:117–122CrossRefGoogle Scholar
  83. 83.
    de Tommaso M, Di Fruscolo O, Sciruicchio V, Specchio N, Livrea P (2007) Two years’ followup of Rivastigmine treatment in Huntington disease. Clin Neuropharmacol 30(1):43–46PubMedCrossRefGoogle Scholar
  84. 84.
    Bonelli RM, Hofmann PA (2007) Systematic review of the treatment studies in Huntington’s disease since 1990. Expert Opin Pharmacother 8(2):141–153PubMedCrossRefGoogle Scholar
  85. 85.
    Paulson HL, Albin RL (2011b) Chapter 1 Huntington’s disease - clinical features and routes to therapy. In Huntington’s disease neurobiology of Huntington's disease. CRC Press, Boca Raton, pp 1–35Google Scholar
  86. 86.
    Graham RK, Deng Y, Slow EJ, Haigh B, Bissada N, Lu G (2006) Cleavage at the caspase6 site is required for neuronal dysfunction and degeneration due to mutant Huntington. Cell 125(6):1179–1191PubMedCrossRefGoogle Scholar
  87. 87.
    Chiò A, Logroscino G, Traynor BJ, Collins J, Simeone JC, Goldstein LA, White LA (2013) Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology 41(2):118–130PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Rossi FH, Franco MC, Estevez AG (2013) Chapter 1 - pathophysiology of amyotrophic lateral sclerosis in current advances in amyotrophic lateral sclerosis. Intech publisher, Rijeka, pp 1–34Google Scholar
  89. 89.
    Amyotrophic Lateral Sclerosis (ALS) - fact sheet (2013) U.S. department of health and human services, public health service, National Institutes of Health, NIH Publication No. 13 916, May 2013
  90. 90.
    Towne C, Setola V, Schneider BL, Aebischer P (2011) Neuroprotection by gene therapy targeting mutant SOD1 in individual pools of motor neurons does not translate into therapeutic benefit in fALS mice. Mol Ther 19(2):274–283PubMedCrossRefGoogle Scholar
  91. 91.
    Nanou A, Higginbottom A, Valori CF, Wyles M, Ning K, Shaw P, Azzouz M (2013) Viral delivery of antioxidant genes as a therapeutic strategy in experimental models of amyotrophic lateral sclerosis. Mol Ther 21(8):1486–1496PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Lagier-Tourenne C, Baughn M, Rigo F, Sun S, Liu P, Li HR, Jiang J, Watt AT, Chun S, Katz M, Qiu J et al (2013) Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. PNAS 110(47):E4530–E4539PubMedCrossRefGoogle Scholar
  93. 93.
    Bergeron D, Lapointe C, Bissonnette C, Tremblay G, Motard J, Roucou X (2013) An out-of-frame overlapping reading frame in the ataxin-1 coding sequence encodes a novel ataxin-1 interacting protein. J Biol Chem 288(30):21824–21835PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M et al (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299:256–259PubMedCrossRefGoogle Scholar
  95. 95.
    Brun A (1987) Frontal lobe degeneration of nonAlzheimer type. I. Neuropathology. Arch Gerontol Geriatr 6:193–208PubMedCrossRefGoogle Scholar
  96. 96.
    Burchell VS, Nelson DE, Sanchez-Martinez A, Delgado-Camprubi M, Ivatt RM, Pogson JH, Randle SJ, Wray S, Lewis PA, Houlden H et al (2013) The Parkinson’s disease-linked proteins Fbxo7 and parkin interact to mediate mitophagy. Nat Neurosci 16(9):1257–1265PubMedCrossRefGoogle Scholar
  97. 97.
    Cardone F, Principe S, Schininà ME, Maras B, Capellari S, Parchi P, Notari S, Di Francesco L, Poleggi A, Galeno R et al (2014) Mutant PrPCJD prevails over wild-type PrPCJD in the brain of V210I and R208H genetic Creutzfeldt-Jakob disease patients. Biochem Biophys Res Commun 454(2):289–294PubMedCrossRefGoogle Scholar
  98. 98.
    Chou AH, Chen YL, Hu SH, Chang YM, Wang HL (2014) Polyglutamine-expanded ataxin-3 impairs long-term depression in Purkinje neurons of SCA3 transgenic mouse by inhibiting HAT and impairing histone acetylation. Brain Res 1583:220–229PubMedCrossRefGoogle Scholar
  99. 99.
    Farg MA, Sundaramoorthy V, Sultana JM, Yang S, Atkinson RA, Levina V, Halloran MA, Gleeson PA, Blair IP, Soo KY, King AE, Atkin JD (2014) C9orf72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking. Hum Mol Genet 23(13):3579–3595PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Forabosco P, Ramasamy A, Trabzuni D, Walker R, Smith C, Bras J, Levine A, Hardy J, Pocock JM, Guerreiro R et al (2013) Insights into TREM2 biology by network analysis of human brain gene expression data. Neurobiol Aging 34:2699–2714PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L et al (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349:704–706PubMedCrossRefGoogle Scholar
  102. 102.
    Ingelsson M, Hyman BT (2002) Disordered proteins in dementia. Ann Med 34:259–271PubMedCrossRefGoogle Scholar
  103. 103.
    Kato S, Shaw P, Wood-Allum C, Leigh PN, Shaw C (2003) Amyotrophic lateral sclerosis. In: Dickson D (ed) Neurodegeneration — the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 350–368Google Scholar
  104. 104.
    Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N, Kitada T (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605–608PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu CE, Jondro PD, Schmidt SD, Wang K et al (1995) Candidate gene for the chromosome 1 familial Alzheimer’s disease locus. Science 269:973–977PubMedCrossRefGoogle Scholar
  106. 106.
    Morris HR, Baker M, Yasojima K, Houlden H, Khan MN, Wood NW, Hardy J, Grossman M, Trojanowski J, Revesz T et al (2002) Analysis of tau haplotypes in Pick’s disease. Neurology 59(3):443–445PubMedCrossRefGoogle Scholar
  107. 107.
    Neuenschwander AG, Thai KK, Figueroa KP, Pulst SM (2014) Amyotrophic lateral sclerosis risk for spinocerebellar ataxia type 2 ATXN2 CAG repeat alleles: a meta-analysis. JAMA Neurol 71(12):1529–1534PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Paisán-Ruíz C, Jain S, Evans EW, Gilks WP, Simón J, van der Brug M, López de Munain A, Aparicio S, Gil AM, Khan N et al (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron 44:595–600PubMedCrossRefGoogle Scholar
  109. 109.
    Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276:2045–2047PubMedCrossRefGoogle Scholar
  110. 110.
    Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T et al (1995) Familial Alzheimer’s disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer’s disease type 3 gene. Nature 376:775–778PubMedCrossRefGoogle Scholar
  111. 111.
    Savinkova L, Drachkova I, Arshinova T, Ponomarenko P, Ponomarenko M, Kolchanov N (2013) An experimental verification of the predicted effects of promoter TATA-box polymorphisms associated with human diseases on interactions between the TATA boxes and TATA-binding protein. PLoS One 8(2):e54626PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Schmechel DE, Saunders AM, Strittmatter WJ, Crain BJ, Hulette CM, Joo SH, Pericak-Vance MA, Goldgaber D, Roses AD (1993) Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in lateonset Alzheimer disease. PNAS 90:9649–9653PubMedCrossRefGoogle Scholar
  113. 113.
    Schneider SA, Marshall KE, Xiao J, LeDoux MS (2012) JPH3 repeat expansions cause a progressive akinetic-rigid syndrome with severe dementia and putaminal rim in a five-generation African-American family. Neurogenetics 13(2):133–140PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K et al (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375:754–760PubMedCrossRefGoogle Scholar
  115. 115.
    Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. PNAS 90:1977–1981PubMedCrossRefGoogle Scholar
  116. 116.
    Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG et al (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304:1158–1160PubMedCrossRefGoogle Scholar
  117. 117.
    Yapijakis C, Gatzonis S, Youroukos S, Kollia V, Karachristianou S, Anagnostouli M (2014) Juvenile myoclonic epilepsy is not associated with the DRPLA gene in a European population. In Vivo 28(6):1193–1196PubMedGoogle Scholar
  118. 118.
    Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ et al (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44:601–607PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Ravindra V. Badhe
    • 1
  • Dharmesh R. Chejara
    • 1
  • Pradeep Kumar
    • 1
  • Yahya E. Choonara
    • 1
  • Viness Pillay
    • 1
    Email author
  1. 1.Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa

Personalised recommendations