The molecular mechanisms of Huntington's disease and its advances in therapeutic strategies

Chinese Journal of Contemporary Neurology and Neurosurgery

Volumn 11, Issue 1, 2011, Pages 30-35

  Yan, Yaping ^a   Zhang, Baorong ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA;

ARTICLE; HUNTINGTON CHOREA; MOLECULAR PATHOLOGY;

EID: 79955541896     PISSN: 16726731     EISSN: None     Source Type: Journal    
DOI: 10.3969/j.issn.1672-6731.2011.01.008     Document Type: Article

References (91)

1. The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell, 1993, 72:971-983.
2. Auerbach W, Hurlbert MS, Hilditch-Maguire P, et al. The HD mutation causes progressive lethal neurological disease in mice expressing reduced levels of huntingtin. Hum Mol Genet, 2001, 10:2515-2523. (Pubitemid 33095002)
3. White JK, Auerbach W, Duyao MP, et al. Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion. Nat Cenet, 1997, 17:404-410. (Pubitemid 27518388)
4. Leavitt BR, Guttman JA, Hodgson JG, et al. Wild - type huntingtin reduces the cellular toxicity of mutant huntingtin in vivo. Am J Hum Genet, 2001, 68:313-324. (Pubitemid 32147802)
5. Ho LW, Brown R, Maxwell M, et al. Wild type Huntingtin reduces the cellular toxicity of mutant Huntingtin in mammalian cell models of Huntington's disease. J Med Genet, 2001, 38:450-452. (Pubitemid 32661206)
6. Leavitt BR, van Raamsdonk JM, Shehadeh J, et al. Wild-type huntingtin protects neurons from excitotoxicity. J Neurochem, 2006, 96:1121-1129.
7. Zhang Y, Leavitt BR, van Raamsdonk JM, et al. Huntingtin inhibits caspase-3 activation. EMBO J, 2006, 25:5896-5906. (Pubitemid 44967772)
8. Zuccato C, Cattaneo E. Role of brain - derived neurotrophic factor in Huntington's disease. Prog Neurobiol, 2007, 81(5/6): 294-330. (Pubitemid 46528643)
9. Fusco FR, Chen Q, Lamoreaux WJ, et al. Cellular localization of huntingtin in striatal and cortical neurons in rats: lack of correlation with neuronal vulnerability in Huntington's disease. J Neurosci, 1999, 19:1189-1202. (Pubitemid 29088902)
10. Gharami K, Xie Y, An JJ, et al. Brain - derived neurotrophic factor over-expression in the forebrain ameliorates Huntington's disease phenotypes in mice. J Neurochem, 2008, 105:369-379. (Pubitemid 351490006)
11. Baquet ZC, Gorski JA, Jones KR. Early striatal dendrite deficits followed by neuron loss with advanced age in the absence of anterograde cortical brain - derived neurotrophic factor. J Neurosci, 2004, 24:4250-4258. (Pubitemid 38620801)
12. Gauthier LR, Charrin BC, Borrell - Pages M, et al. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell, 2004, 118:127-138.
13. Zuccato C, Ciammola A, Rigamonti D, et al. Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science, 2001, 293:493-498. (Pubitemid 32679077)
14. Zuccato C, Belyaev N, Conforti P, et al. Widespread disruption of repressor element - 1 silencing transcription factor/neuron - restrictive silencer factor occupancy at its target genes in Huntington's disease. J Neurosci, 2007, 27:6972-6983. (Pubitemid 47015906)
15. Zuccato C, Tartari M, Crotti A, et al. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat Genet, 2003, 35:76-83. (Pubitemid 37048599)
16. Diekmann H, Anichtchik O, Fleming A, et al. Decreased BDNF levels are a major contributor to the embryonic phenotype of huntingtin knockdown zebrafish. J Neurosci, 2009, 29:1343-1349.
17. Shimojo M. Huntingtin regulates REl - silencing transcription factor/neuron - restrictive silencer factor (REST/NRSF) nuclear trafficking indirectly through a complex with REST/NRSF - interacting LIM domain protein (RILP) and dynactin p150 Glued. J Biol Chem, 2008, 283:34880-34886.
18. Velier J, Kim M, Schwarz C, et al. Wild - type and mutant huntingtins function in vesicle trafficking in the secretory and endocytic pathways. Exp Neurol, 1998, 152:34-40. (Pubitemid 28366964)
19. Trushina E, Dyer RB, Badger JD 2nd, et al. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol Cell Biol, 2004, 24:8195-8209. (Pubitemid 39167467)
20. Strand AD, Baquet ZC, Aragaki AK, et al. Expression profiling of Huntington's disease models suggests that brain - derived neurotrophic factor depletion plays a major role in striatal degeneration. J Neurosci, 2007, 27:11758-11768. (Pubitemid 350006916)
21. Canals JM, Pineda JR, Torres - Peraza JF, et al. Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington's disease. J Neurosci, 2004, 24:7727-7739. (Pubitemid 39186828)
22. DiFiglia M. Excitotoxic injury of the neostriatum: a model for Huntington's disease. Trends Neurosci, 1990, 13:286-289. (Pubitemid 20193460)
23. Goldberg YP, Nicholson DW, Rasper DM, et al. Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet, 1996, 13:442-449.
24. Graham RK, Deng Y, Slow EJ, et al. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell, 2006, 125:1179-1191. (Pubitemid 43866195)
25. Hermel E, Gafni J, Propp SS, et al. Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease. Cell Death Differ, 2004, 11:424-438. (Pubitemid 38489420)
26. Wellington CL, Singaraja R, Ellerby L, et al. Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells. J Biol Chem, 2000, 275: 19831-19838. (Pubitemid 30441585)
27. Davies SW, Turmaine M, Cozens BA, et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 1997, 90:537-548. (Pubitemid 27347243)
28. DiFiglia M, Sapp E, Chase KO, et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neuntes in brain. Science, 1997, 277:1990-1993. (Pubitemid 27449140)
29. Luo S, Vacher C, Davies JE, et al. Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity. J Cell Biol, 2005, 169:647-656. (Pubitemid 41002857)
30. Warby SC, Chan EY, Metzler M, et al. Huntingtin phosphorylation on serine 421 is significantly reduced in the striatum and by polyglutamine expansion in vivo. Hum Mol Genet, 2005, 14:1569-1577. (Pubitemid 40823464)
31. Yang W, Dunlap JR, Andrews RB, et al. Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells. Hum Mol Genet, 2002, 11:2905-2917.
32. Cha JH. Transcriptional signatures in Huntington's disease. Prog Neurobiol, 2007, 83:228-248.
33. Nucifora FC Jr, Ellerby LM, Wellington CL, et al. Nuclear localization of a non-caspase truncation product of atrophin-1, with an expanded polyglutamine repeat, increases cellular toxicity. J Biol Chem, 2003, 278:13047-13055. (Pubitemid 36800072)
34. Yamamoto A, Lucas JJ, Hen R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell, 2000, 101:57-66.
35. Tydlacka S, Wang CE, Wang X, et al. Differential activities of the ubiquitin - proteasome system in neurons versus glia may account for the preferential accumulation of misfolded proteins in neurons. J Neurosci, 2008, 28:13285-13295.
36. Vacher C, Garcia-Oroz L, Rubinsztein DC. Overexpression of yeast hsp104 reduces polyglutamine aggregation and prolongs survival of a transgenic mouse model of Huntington's disease. Hum Mol Genet, 2005, 14:3425-3433. (Pubitemid 41672126)
37. Warrick JM, Chan HY, Gray-Board GL, et al. Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat Genet, 1999, 23:425-428.
38. Bhutani N, Venkatraman P, Goldberg AL. Puromycin-sensitive aminopeptidase is the major peptidase responsible for digesting polyglutamine sequences released by proteasomes during protein degradation. EMBO J, 2007, 26:1385-1396. (Pubitemid 46398712)
39. Kuemmerle S, Gutekunst CA, Klein AM, et al. Huntington aggregates may not predict neuronal death in Huntington's disease. Ann Neurol, 1999, 46:842-849.
40. Saudou F, Finkbeiner S, Devys D, et al. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell, 1998, 95:55-66.
41. Bodner RA, Outeiro TF, Altmann S, et al. Pharmacological promotion of inclusion formation: a therapeutic approach for Huntington's and Parkinson's diseases. Proc Natl Acad Sci USA, 2006, 103:4246-4251.
42. Slow EJ, Graham RK, Osmand AP, et al. Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions. Proc Natl Acad Sci USA, 2005, 102:11402-11407. (Pubitemid 41153832)
43. Moffitt H, McPhail GD, Woodman B, et al. Formation of polyglutamine inclusions in a wide range of non-CNS tissues in the HdhQ150 knock-in mouse model of Huntington's disease. PLoS One, 2009, 4:E8025.
44. Sathasivam K, Hobbs C, Turmaine M, et al. Formation of polyglutamine inclusions in non-CNS tissue. Hum Mol Genet, 1999, 8:813-822. (Pubitemid 29189048)
45. Arrasate M, Mitra S, Schweitzer ES, et al. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature, 2004, 431:805-810. (Pubitemid 39434070)
46. Bennett EJ, Shaler TA, Woodman B, et al. Global changes to the ubiquitin system in Huntington's disease. Nature, 2007, 448: 704-708. (Pubitemid 47236860)
47. Ravikumar B, Vacher C, Berger Z, et al. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Cenet, 2004, 36:585-595. (Pubitemid 38715985)
48. Ventruti A, Cuervo AM. Autophagy and neurodegeneration. Curr Neurol Neurosci Rep, 2007, 7:443-451. (Pubitemid 47422787)
49. Kegel KB, Kim M, Sapp E, et al. Huntingtin expression stimulates endosomal - lysosomal activity, endosome tubulation, and autophagy. J Neurosci, 2000, 20:7268-7278.
50. Jeong H, Then F, Melia TJ Jr, et al. Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell, 2009, 137: 60-72.
51. Orr AL, Li S, Wang CE, et al. N-terminal mutant huntingtin associates with mitochondria and impairs mitochondrial trafficking. J Neurosci, 2008, 28:2783-2792. (Pubitemid 351398886)
52. Thompson LM, Aiken CT, Kaltenbach LS, et al. IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome. J Cell Biol, 2009, 187:1083-1099.
53. Cuervo AM, Dice JF. Regulation of lamp2a levels in the lysosomal membrane. Traffic, 2000, 1:570-583.
54. Gárdián G, Vécsei L. Huntington's disease: pathomechanism and therapeutic perspectives. J Neural Transm, 2004, 111(10/11):1485-1494. (Pubitemid 39468401)
55. Goebel HH, Heipertz R, Scholz W, et al. Juvenile Huntington chorea: clinical, ultrastructural, and biochemical studies. Neurology, 1978, 28:23-31. (Pubitemid 8272515)
56. Jenkins BG, Koroshetz WJ, Beal MF, et al. Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy. Neurology, 1993, 43:2689-2695. (Pubitemid 24004570)
57. Moffett JR, Ross B, Arun P, et al. N - Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol, 2007, 81:89-131.
58. Kuhl DE, Markham CH, Metter EJ, et al. Local cerebral glucose utilization in symptomatic and presymptomatic Huntington's disease. Res Publ Assoc Res Nerv Ment Dis, 1985, 63:199-209.
59. Browne SE. Mitochondria and Huntington's disease pathogenesis: insight from genetic and chemical models. Ann NY Acad Sci, 2008, 1147:358-382.
60. Feigin A, Leenders KL, Moeller JR, et al. Metabolic network abnormalities in early Huntington's disease: an [(18)F]FDG PET study. J Nucl Med, 2001, 42:1591-1595. (Pubitemid 33131316)
61. Butterfield DA, Howard BJ, LaFontaine MA. Brain oxidative stress in animal models of accelerated aging and the age-related neurodegenerative disorders, Alzheimer's disease and Huntington's disease. Curr Med Chem, 2001, 8:815-828.
62. Panov AV, Gutekunst CA, Leavitt BR, et al. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat Neurosci, 2002, 5:731-736. (Pubitemid 34827590)
63. Arzberger T, Krampfl K, Leimgruber S, et al. Changes of NMDA receptor subunit (NR1, NR2B) and glutamate transporter (GLT1) mRNA expression in Huntington's disease: an in situ hybridization study. J Neuropathol Exp Neurol, 1997, 56:440-454. (Pubitemid 27465027)
64. Augood SJ, Faull RL, Emson PC. Dopamine D1 and D2 receptor gene expression in the striatum in Huntington's disease. Ann Neurol, 1997, 42:215-221. (Pubitemid 27340467)
65. Augood SJ, Faull RL, Love DR, et al. Reduction in enkephalin and substance P messenger RNA in the striatum of early grade Huntington's disease: a detailed cellular in situ hybridization study. Neuroscience, 1996, 72:1023-1036. (Pubitemid 26135583)
66. Norris PJ, Waldvogel HJ, Faull RL, et al. Decreased neuronal nitric oxide synthase messenger RNA and somatostatin messenger RNA in the striatum of Huntington's disease. Neuroscience, 1996, 72:1037-1047. (Pubitemid 26135584)
67. Cha JH, Frey AS, Alsdorf SA, et al. Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease. Philos Trans R Soc Lond B Biol Sci, 1999, 354:981-989. (Pubitemid 29477958)
68. Cha JH, Kosinski CM, Kerner JA, et al. Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci USA, 1998, 95:6480-6485. (Pubitemid 28249039)
69. Zuccato C, Valenza M, Cattaneo E. Molecular mechanisms and potential therapeutical targets in Huntington's disease. Physiol Rev, 2010, 90:905-981.
70. Squitieri F, Ciammola A, Colonnese C, et al. Neuroprotective effects of riluzole in Huntington's disease. Eur J Nucl Med Mol Imaging, 2008, 35:221-222. (Pubitemid 50001344)
71. Seppi K, Mueller J, Bodner T, et al. Riluzole in Huntington's disease (HD): an open label study with one year follow up. J Neurol, 2001, 248:866-869. (Pubitemid 32955670)
72. Lee ST, Chu K, Park JE, et al. Memantine reduces striatal cell death with decreasing calpain level in 3-nitropropionic model of Huntington's disease. Brain Res, 2006, 1118:199-207. (Pubitemid 44633871)
73. Frank S, Ondo W, Fahn S, et al. A study of chorea after tetrabenazine withdrawal in patients with Huntington disease. Clin Neuropharmacol, 2008, 31:127-133. (Pubitemid 351787108)
74. Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology, 2006, 66:366-372.
75. Zuccato C, Cattaneo E. Brain - derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol, 2009, 5:311-322.
76. Pérez-Navarro E, Canudas AM, Akerund P, et al. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 prevent the death of striatal projection neurons in a rodent model of Huntington's disease. J Neurochem, 2000, 75:2190-2199.
77. Chen M, Ona VO, Li M, et al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med, 2000, 6:797-801. (Pubitemid 30469429)
78. Aubry L, Bugi A, Lefort N, et al. Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats. Proc Natl Acad Sci USA, 2008, 105:16707-16712.
79. Bonelli RM, Hodl AK, Hofmann P, et al. Neuroprotection in Huntington's disease: a 2-year study on minocycline. Int Clin Psychopharmacol, 2004, 19:337-342. (Pubitemid 39506988)
80. Wood NI, Pallier PN, Wanderer J, et al. Systemic administration of Congo red does not improve motor or cognitive function in R6/2 mice. Neurobiol Dis, 2007, 25:342-353. (Pubitemid 46124014)
81. Zhang X, Smith DL, Meriin AB, et al. A potent small molecule inhibits polyglutamine aggregation in Huntington's disease neurons and suppresses neurodegeneration in vivo. Proc Natl Acad Sci USA, 2005, 102:892-897. (Pubitemid 40282761)
82. Ehrnhoefer DE, Duennwald M, Markovic P, et al. Green tea (-)-epigallocatechin - gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington's disease models. Hum Mol Genet, 2006, 15:2743-2751. (Pubitemid 44400401)
83. Ferrante RJ, Andreassen OA, Jenkins BG, et al. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J Neurosci, 2000, 20:4389-4397. (Pubitemid 30396603)
84. Tabrizi SJ, Blamire AM, Manners DN, et al. High-dose creatine therapy for Huntington disease: a 2 - year clinical and MRS study. Neurology, 2005, 64:1655-1656. (Pubitemid 40617715)
85. Hogarth P, Lovrecic L, Krainc D. Sodium phenylbutyrate in Huntington's disease: a dose-finding study. Mov Disord, 2007, 22:1962-1964.
86. Butler R, Bates GP. Histone deacetylase inhibitors as therapeutics for polyglutamine disorders. Nat Rev Neurosci, 2006, 7:784-796. (Pubitemid 44435261)
87. Southwell AL, Ko J, Patterson PH. Intrabody gene therapy ameliorates motor, cognitive, and neuropathological symptoms in multiple mouse models of Huntington's disease. J Neurosci, 2009, 29:13589-13602.
88. Bachoud-Lévi AC, Gaura V, Brugières P, et al. Effect of fetal neural transplants in patients with Huntington's disease 6 years after surgery: a long-term follow-up study. Lancet Neurol, 2006, 5:303-309.