Therapeutic Prospects for Polyglutamine Disease

Protein Misfolding Diseases: Current and Emerging Principles and Therapies

Volumn , Issue , 2010, Pages 887-902

  Pennuto, Maria ^a   Fischbeck, Kenneth H ^b  

^a ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

^b NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

Author keywords

Gsk 3b, implicated in neurodegenerative disorders, and HD establishing potential of lithium as treatment for HD; polyglutamine disease, family of inherited, late onset, progressive neurodegenerative disorders therapeutic prospects; reducing polyglutamine protein expression disease manifestations reversed by blocking mutant protein expression

Indexed keywords

EID: 84878886819     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470572702.ch40     Document Type: Chapter

References (96)

1. Zu, T., Duvick, L.A., Kaytor, M.D., Berlinger, M.S., Zoghbi, H.Y., Clark, H.B., Orr, H.T. (2004). Recovery from polyglutamine-induced neurodegeneration in conditional SCA1 transgenic mice. J Neurosci, 24, 8853-8861.
2. Yamamoto, A., Lucas, J.J., Hen, R. (2000). Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell, 101, 57-66.
3. Boado, R.J., Kazantsev, A., Apostol, B.L., Thompson, L.M., Pardridge, W.M. (2000). Antisense-mediated down-regulation of the human huntingtin gene. J Pharmacol Exp Ther, 295, 239-243.
4. Nellemann, C., Abell, K., Nørremølle, A., Løkkegaard, T., Naver, B., Röpke, C., Rygaard, J., Sørensen, S.A., Hasholt, L. (2000). Inhibition of Huntington synthesis by antisense oligodeoxynucleotides. Mol Cell Neurosci, 16, 313-323.
5. Yen, L., Strittmatter, S.M., Kalb, R.G. (1999). Sequence-specific cleavage of Huntingtin mRNA by catalytic DNA. Ann Neurol, 46, 366-373.
6. Caplen, N.J., Taylor, J.P., Statham, V.S., Tanaka, F., Fire, A., Morgan, R.A. (2002). Rescue of polyglutamine-mediated cytotoxicity by double-stranded RNAmediated RNA interference. Hum Mol Genet, 11, 175-184.
7. Xia, H., Mao, Q., Eliason, S.L., Harper, S.Q., Martins, I.H., Orr, H.T., Paulson, H.L., Yang, L., Kotin, R.M., Davidson, B.L. (2004). RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat Med, 10, 816-820.
8. Wang, Y.L., Liu, W., Wada, E., Murata, M., Wada, K., Kanazawa, I. (2005). Clinico-pathological rescue of a model mouse of Huntington's disease by siRNA. Neurosci Res, 53, 241-249.
9. Harper, S.Q., Staber, P.D., He, X., Eliason, S.L., Martins, I.H., Mao, Q., Yang, L., Kotin, R.M., Paulson, H.L., Davidson, B.L. (2005). RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model. Proc Natl Acad Sci U S A, 102, 5820-5825.
10. Rodriguez-Lebron, E., Denovan-Wright, E.M., Nash, K., Lewin, A.S., Mandel, R.J. (2005). Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington's disease transgenic mice. Mol Ther, 12, 618-633.
11. Gary, D.S., Davidson, A., Milhavet, O., Slunt, H., Borchelt, D.R. (2007). Investigation of RNA interference to suppress expression of full-length and fragment human huntingtin. Neuromolecular Med, 9, 145-155.
12. Hegde, A.N., Upadhya, S.C. (2007). The ubiquitin-proteasome pathway in health and disease of the nervous system. Trends Neurosci, 30, 587-595.
13. Shacka, J.J., Roth, K.A., Zhang, J. (2008). The autophagy-lysosomal degradation pathway, role in neurodegenerative disease and therapy. Front Biosci, 13, 718-736.
14. Ding, W.X., Ni, H.M., Gao, W., Yoshimori, T., Stolz, D.B., Ron, D., Yin, X.M. (2007). Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am J Pathol, 171, 513-524.
15. Pandey, U.B., Nie, Z., Batlevi, Y., McCray, B.A., Ritson, G.P., Nedelsky, N.B., Schwartz, S.L., DiProspero, N.A., Knight, M.A., Schuldiner, O., Padmanabhan, R., Hild, M., Berry, D.L., Garza, D., Hubbert, C.C., Yao, T.P., Baehrecke, E.H., Taylor, J.P. (2007). HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature, 447, 859-863.
16. Bence, N.F., Sampat, R.M., Kopito, R.R. (2001). Impairment of the ubiquitinproteasome system by protein aggregation. Science, 292, 1552-1555.
17. Bennett, E.J., Shaler, T.A., Woodman, B., Ryu, K.Y., Zaitseva, T.S., Becker, C.H., Bates, G.P., Schulman, H., Kopito, R.R. (2007). Global changes to the ubiquitin system in Huntington's disease. Nature, 448, 704-708.
18. Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., Tanaka, K. (2006). Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature, 441, 880-884.
19. Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., Mizushima, N. (2006). Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature, 441, 885-889.
20. Cummings, C.J., Mancini, M.A., Antalffy, B., DeFranco, D.B., Orr, H.T., Zoghbi, H.Y. (1998). Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nat Genet, 19, 148-154.
21. Chai, Y., Koppenhafer, S.L., Bonini, N.M., Paulson, H.L. (1999). Analysis of the role of heat shock protein (Hsp). molecular chaperones in polyglutamine disease. J Neurosci, 19, 10338-10347.
22. Wyttenbach, A., Sauvageot, O., Carmichael, J., Diaz-Latoud, C., Arrigo, A.P., Rubinsztein, D.C. (2002). Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin. Hum Mol Genet, 11, 1137-1151.
23. Ishihara, K., Yamagishi, N., Saito, Y., Adachi, H., Kobayashi, Y., Sobue, G., Ohtsuka, K., Hatayama, T. (2003). Hsp105alpha suppresses the aggregation of truncated androgen receptor with expanded CAG repeats and cell toxicity. J Biol Chem, 278, 25143-25150.
24. Adachi, H., Katsuno, M., Minamiyama, M., Sang, C., Pagoulatos, G., Angelidis, C., Kusakabe, M., Yoshiki, A., Kobayashi, Y., Doyu, M., Sobue, G. (2003). Heat shock protein 70 chaperone overexpression ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model by reducing nuclear-localized mutant androgen receptor protein. J Neurosci, 23, 2203-2211.
25. Cummings, C.J., Sun, Y., Opal, P., Antalffy, B., Mestril, R., Orr, H.T., Dillmann, W.H., Zoghbi, H.Y. (2001). Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice. Hum Mol Genet, 10, 1511-1518.
26. Vacher, C., Garcia-Oroz, L., Rubinsztein, D.C. (2005). Overexpression of yeast hsp104 reduces polyglutamine aggregation and prolongs survival of a transgenic mouse model of Huntington's disease. Hum Mol Genet, 14, 3425-3433.
27. Adachi, H., Waza, M., Tokui, K., Katsuno, M., Minamiyama, M., Tanaka, F., Doyu, M., Sobue, G. (2007). CHIP overexpression reduces mutant androgen receptor protein and ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model. J Neurosci, 27, 5115-5126.
28. Al-Ramahi, I., Lam, Y.C., Chen, H.K., de Gouyon, B., Zhang, M., Pérez, A.M., Branco, J., de Haro, M., Patterson, C., Zoghbi, H.Y., Botas, J. (2006). CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation. J Biol Chem, 281, 26714-26724.
29. Miller, V.M., Nelson, R.F., Gouvion, C.M., Williams, A., Rodriguez-Lebron, E., Harper, S.Q., Davidson, B.L., Rebagliati, M.R., Paulson, H.L. (2005). CHIP suppresses polyglutamine aggregation and toxicity in vitro and in vivo. J Neurosci, 25, 9152-9161.
30. Katsuno, M., Sang, C., Adachi, H., Minamiyama, M., Waza, M., Tanaka, F., Doyu, M., Sobue, G. (2005). Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron disease. Proc Natl Acad Sci U S A, 102, 16801-16806.
31. Sittler, A., Lurz, R., Lueder, G., Priller, J., Lehrach, H., Hayer-Hartl, M.K., Hartl, F.U., Wanker, E.E. (2001). Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease. Hum Mol Genet, 10, 1307-1315.
32. Waza, M., Adachi, H., Katsuno, M., Minamiyama, M., Sang, C., Tanaka, F., Inukai, A., Doyu, M., Sobue, G.. (2005). 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. Nat Med, 11, 1088-1095.
33. Herbst, M., Wanker, E.E. (2007). Small molecule inducers of heat-shock response reduce polyglutamine-mediated huntingtin aggregation: a possible therapeutic strategy. Neurodegener Dis, 4, 254-260.
34. Ravikumar, B., Vacher, C., Berger, Z., Davies, J.E., Luo, S., Oroz, L.G., Scaravilli, F., Easton, D.F., Duden, R., O'Kane, C.J., Rubinsztein, D.C. (2004). Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet, 36, 585-595.
35. Berger, Z., Ravikumar, B., Menzies, F.M., Oroz, L.G., Underwood, B.R., Pangalos, M.N., Schmitt, I., Wullner, U., Evert, B.O., O'Kane, C.J., Rubinsztein, D.C. (2006). Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum Mol Genet, 15, 433-442.
36. Sarkar, S., Perlstein, E.O., Imarisio, S., Pineau, S., Cordenier, A., Maglathlin, R.L., Webster, J.A., Lewis, T.A., O'Kane, C.J., Schreiber, S.L., Rubinsztein, D.C. (2007). Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat Chem Biol, 3, 331-338.
37. Steffan, J.S., Bodai, L., Pallos, J., Poelman, M., McCampbell, A., Apostol, B.L., Kazantsev, A., Schmidt, E., Zhu, Y.Z., Greenwald, M., Kurokawa, R., Housman, D.E., Jackson, G.R., Marsh, J.L., Thompson, L.M. (2001). Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature, 413, 739-743.
38. Taylor, J.P., Taye, A.A., Campbell, C., Kazemi-Esfarjani, P., Fischbeck, K.H., Min, K.T. (2003). Aberrant histone acetylation, altered transcription, and retinal degeneration in a Drosophila model of polyglutamine disease are rescued by CREB-binding protein. Genes Dev, 17, 1463-1468.
39. Nucifora, F.C. Jr., Sasaki, M., Peters, M.F., Huang, H., Cooper, J.K., Yamada, M., Takahashi, H., Tsuji, S., Troncoso, J., Dawson, V.L., Dawson, T.M., Ross, C.A. (2001). Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science, 291, 2423-2428.
40. McCampbell, A., Taylor, J.P., Taye, A.A., Robitschek, J., Li, M., Walcott, J., Merry, D., Chai, Y., Paulson, H., Sobue, G., Fischbeck, K.H. (2000). CREB-binding protein sequestration by expanded polyglutamine. Hum Mol Genet, 9, 2197-2202.
41. Ferrante, R.J., Kubilus, J.K., Lee, J., Ryu, H., Beesen, A., Zucker, B., Smith, K., Kowall, N.W., Ratan, R.R., Luthi-Carter, R., Hersch, S.M. (2003). Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice. J Neurosci, 23, 9418-9427.
42. Ying, M., Xu, R., Wu, X., Zhu, H., Zhuang, Y., Han, M., Xu, T. (2006). Sodium butyrate ameliorates histone hypoacetylation and neurodegenerative phenotypes in a mouse model for DRPLA. J Biol Chem, 281, 12580-12586.
43. Minamiyama, M., Katsuno, M., Adachi, H., Waza, M., Sang, C., Kobayashi, Y., Tanaka, F., Doyu, M., Inukai, A., Sobue, G. (2004). Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Hum Mol Genet, 13, 1183-1192.
44. Hockly, E., Richon, V.M., Woodman, B., Smith, D.L., Zhou, X., Rosa, E., Sathasivam, K., Ghazi-Noori, S., Mahal, A., Lowden, P.A., Steffan, J.S., Marsh, J.L., Thompson, L.M., Lewis, C.M., Marks, P.A., Bates, GP. (2003). Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease. Proc Natl Acad Sci U S A, 100, 2041-2046.
45. Gardian, G., Browne, S.E., Choi, D.K., Klivenyi, P., Gregorio, J., Kubilus, J.K., Ryu, H., Langley, B., Ratan, R.R., Ferrante, R.J., Beal, M.F. (2005). Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington's disease. J Biol Chem, 280, 556-563.
46. Sánchez, I., Xu, C.J., Juo, P., Kakizaka, A., Blenis, J., Yuan, J. (1999). Caspase-8 is required for cell death induced by expanded polyglutamine repeats. Neuron, 22, 623-633.
47. Ona, V.O., Li, M., Vonsattel, J.P., Andrews, L.J., Khan, S.Q., Chung, W.M., Frey, A.S., Menon, A.S., Li, X.J., Stieg, P.E., Yuan, J., Penney, J.B., Young, A.B., Cha, J.H., Friedlander, R.M. (1999). Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature, 399, 263-267.
48. Chen, M., Ona, V.O., Li, M., Ferrante, R.J., Fink, K.B., Zhu, S., Bian, J., Guo, L., Farrell, L.A., Hersch, S.M., Hobbs, W., Vonsattel, J.P., Cha, J.H., Friedlander, R.M. (2000). Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med, 6, 797-801.
49. Hackam, A.S., Singaraja, R., Wellington, C.L., Metzler, M., McCutcheon, K., Zhang, T., Kalchman, M., Hayden, M.R. (1998). The influence of huntingtin protein size on nuclear localization and cellular toxicity. J Cell Biol, 141, 1097-1105.
50. Wellington, C.L., Ellerby, L.M., Hackam, A.S., Margolis, R.L., Trifiro, M.A., Singaraja, R., McCutcheon, K., Salvesen, G.S., Propp, S.S., Bromm, M., Rowland, K.J., Zhang, T., Rasper, D., Roy, S., Thornberry, N., Pinsky, L., Kakizuka, A., Ross, C.A., Nicholson, D.W., Bredesen, D.E., Hayden, M.R. (1998). Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J Biol Chem, 273, 9158-9167.
51. Haacke, A., Broadley, S.A., Boteva, R., Tzvetkov, N., Hartl, F.U., Breuer, P. (2006). Proteolytic cleavage of polyglutamine-expanded ataxin-3 is critical for aggregation and sequestration of non-expanded ataxin-3. Hum Mol Genet, 15, 555-568.
52. Garden, G.A., Libby, R.T., Fu, Y.H., Kinoshita, Y., Huang, J., Possin, D.E., Smith, A.C., Martinez, R.A., Fine, G.C., Grote, S.K., Ware, C.B., Einum, D.D., Morrison, R.S., Ptacek, L.J., Sopher, B.L., La Spada, A.R. (2002). Polyglutamineexpanded ataxin-7 promotes non-cell-autonomous Purkinje cell degeneration and displays proteolytic cleavage in ataxic transgenic mice. J Neurosci, 22, 4897-4905.
53. Ellerby, L.M., Hackam, A.S., Propp, S.S., Ellerby, H.M., Rabizadeh, S., Cashman, N.R., Trifiro, M.A., Pinsky, L., Wellington, C.L., Salvesen, G.S., Hayden, M.R., Bredesen, D.E. (1999). Kennedy's disease, caspase cleavage of the androgen receptor is a crucial event in cytotoxicity. J Neurochem, 72, 185-195.
54. Ellerby, L.M., Andrusiak, R.L., Wellington, C.L., Hackam, A.S., Propp, S.S., Wood, J.D., Sharp, A.H., Margolis, R.L., Ross, C.A., Salvesen, G.S., Hayden, M.R., Bredesen, D.E. (1999). Cleavage of atrophin-1 at caspase site aspartic acid 109 modulates cytotoxicity. J Biol Chem, 274, 8730-8736.
55. Graham, R.K., Deng, Y., Slow, E.J., Haigh, B., Bissada, N., Lu, G., Pearson, J., Shehadeh, J., Bertram, L., Murphy, Z., Warby, S.C., Doty, C.N., Roy, S., Wellington, C.L., Leavitt, B.R., Raymond, L.A., Nicholson, D.W., Hayden, M.R. (2006). Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell, 125, 1179-1191.
56. Young, J.E., Gouw, L., Propp, S., Sopher, B.L., Taylor, J., Lin, A., Hermel, E., Logvinova, A., Chen, S.F., Chen, S., Bredesen, D.E., Truant, R., Ptacek, L.J., La Spada, A.R., Ellerby, L.M. (2007). Proteolytic cleavage of ataxin-7 by caspase-7 modulates cellular toxicity and transcriptional dysregulation. J Biol Chem, 282, 30150-30160.
57. Gafni, J., Hermel, E., Young, J.E., Wellington, C.L., Hayden, M.R., Ellerby, L.M. (2004). Inhibition of calpain cleavage of huntingtin reduces toxicity, accumulation of calpain/caspase fragments in the nucleus. J Biol Chem, 279, 20211-20220.
58. Zeron, M.M., Hansson, O., Chen, N., Wellington, C.L., Leavitt, B.R., Brundin, P., Hayden, M.R., Raymond, L.A. (2002). Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease. Neuron, 33, 849-860.
59. Lee, S.T., Chu, K., Park, J.E., Kang, L., Ko, S.Y., Jung, K.H., Kim, M. (2006). Memantine reduces striatal cell death with decreasing calpain level in 3-nitropropionic model of Huntington's disease. Brain Res, 1118, 199-207.
60. Yu, Z., Dadgar, N., Albertelli, M., Gruis, K., Jordan, C., Robins, D.M., Lieberman, A.P. (2006). Androgen-dependent pathology demonstrates myopathic contribution to the Kennedy disease phenotype in a mouse knock-in model. J Clin Invest, 116, 2663-2672.
61. Colin, E., Régulier, E., Perrin, V., Dürr, A., Brice, A., Aebischer, P., Déglon, N., Humbert, S., Saudou, F. (2005). Akt is altered in an animal model of Huntington's disease and in patients. Eur J Neurosci, 21, 1478-1488.
62. Humbert, S., Bryson, E.A., Cordelieres, F.P., Connors, N.C., Datta, S.R., Finkbeiner, S., Greenberg, M.E., Saudou, F. (2002). The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt. Dev Cell, 2, 831-837.
63. de Almeida, L.P., Zala, D., Aebischer, P., Déglon, N. (2001). Neuroprotective effect of a CNTF-expressing lentiviral vector in the quinolinic acid rat model of Huntington's disease. Neurobiol Dis, 8, 433-446.
64. Pérez-Navarro, E., Canudas, A.M., Akerund, P., Alberch, J., Arenas, E. (2000). 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, 75, 2190-2199.
65. Bemelmans, A.P., Horellou, P., Pradier, L., Brunet, I., Colin, P., Mallet, J. (1999). Brain-derived neurotrophic factor-mediated protection of striatal neurons in an excitotoxic rat model of Huntington's disease, as demonstrated by adenoviral gene transfer. Hum Gene Ther, 10, 2987-2997.
66. Emerich, D.F., Lindner, M.D., Winn, S.R., Chen, E.Y., Frydel, B.R., Kordower, J.H. (1996). Implants of encapsulated human CNTF-producing fibroblasts prevent behavioral deficits and striatal degeneration in a rodent model of Huntington's disease. J Neurosci, 16, 5168-5181.
67. Ramaswamy, S., McBride, J.L., Herzog, C.D., Brandon, E., Gasmi, M., Bartus, R.T., Kordower, J.H. (2007). Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington's disease. Neurobiol Dis, 26, 375-384.
68. McBride, J.L., Ramaswamy, S., Gasmi, M., Bartus, R.T., Herzog, C.D., Brandon, E.P., Zhou, L., Pitzer, M.R., Berry-Kravis, E.M., Kordower, J.H. (2006). Viral delivery of glial cell line-derived neurotrophic factor improves behavior and protects striatal neurons in a mouse model of Huntington's disease. Proc Natl Acad Sci U S A, 103, 9345-9350.
69. Sopher, B.L., Thomas, P.S. Jr., LaFevre-Bernt, M.A., Holm, I.E., Wilke, S.A., Ware, C.B., Jin, L.W., Libby, R.T., Ellerby, L.M., La Spada, A.R. (2004). Androgen receptor YAC transgenic mice recapitulate SBMA motor neuronopathy and implicate VEGF164 in the motor neuron degeneration. Neuron, 41, 687-699.
70. Palazzolo, I., Burnett, B.G., Young, J.E., Brenne, P.L., La Spada, A.R., Fischbeck, K.H., Howell, B.W., Pennuto, M. (2007). Akt blocks ligand binding and protects against expanded polyglutamine androgen receptor toxicity. Hum Mol Genet, 16, 1593-1603.
71. Palazzolo, I., Stack, C., Kong, L., Musaro, A., Adachi, H., Katsuno, K., Sobue, G., Taylor, J.P., Sumner, C.J., Fischbeck, K.H., Pennuto, M. (2009). Overexpression of IGF-1 in muscle attenuates disease in a mouse model of spinal and bulbar muscular atrophy. Neuron, 63, 316-328.
72. Vig, P.J., Subramony, S.H., D'Souza, D.R., Wei, J., Lopez, M.E. (2006). Intranasal administration of IGF-I improves behavior and Purkinje cell pathology in SCA1 mice. Brain Res Bull, 69, 573-579.
73. Kahlem, P., Green, H., Djian, P. (1998). Transglutaminase action imitates Huntington's disease, selective polymerization of Huntingtin containing expanded polyglutamine. Mol Cell, 1, 595-601.
74. Mandrusiak, L.M., Beitel, L.K., Wang, X., Scanlon, T.C., Chevalier-Larsen, E., Merry, D.E., Trifiro, M.A. (2003). Transglutaminase potentiates ligand-dependent proteasome dysfunction induced by polyglutamine-expanded androgen receptor. Hum Mol Genet, 12, 1497-1506.
75. D'Souza, D.R., Wei, J., Shao, Q., Hebert, M.D., Subramony, S.H., Vig, P.J. (2006). Tissue transglutaminase crosslinks ataxin-1, possible role in SCA1 pathogenesis. Neurosci Lett, 409, 5-9.
76. Lesort, M., Chun, W., Johnson, G.V., Ferrante, R.J. (1999). Tissue transglutaminase is increased in Huntington's disease brain. J Neurochem, 73, 2018-2027.
77. Karpuj, M.V., Garren, H., Slunt, H., Price, D.L., Gusella, J., Becher, M.W., Steinman, L. (1999). Transglutaminase aggregates huntingtin into nonamyloidogenic polymers, and its enzymatic activity increases in Huntington's disease brain nuclei. Proc Natl Acad Sci U S A, 96, 7388-7393.
78. Van Raamsdonk, J.M., Pearson, J., Bailey, C.D., Rogers, D.A., Johnson, G.V., Hayden, M.R., Leavitt, B.R. (2005). Cystamine treatment is neuroprotective in the YAC128 mouse model of Huntington disease. J Neurochem, 95, 210-220.
79. Dedeoglu, A., Kubilus, J.K., Jeitner, T.M., Matson, S.A., Bogdanov, M., Kowall, N.W., Matson, W.R., Cooper, A.J., Ratan, R.R., Beal, M.F., Hersch, S.M., Ferrante, R.J. (2002). Therapeutic effects of cystamine in a murine model of Huntington's disease. J Neurosci, 22, 8942-8950.
80. Mastroberardino, P.G., Iannicola, C., Nardacci, R., Bernassola, F., De Laurenzi, V., Melino, G., Moreno, S., Pavone, F., Oliverio, S., Fesus, L., Piacentini, M. (2002). 'Tissue' transglutaminase ablation reduces neuronal death and prolongs survival in a mouse model of Huntington's disease. Cell Death Differ, 9, 873-880.
81. Igarashi, S., Koide, R., Shimohata, T., Yamada, M., Hayashi, Y., Takano, H., Date, H., Oyake, M., Sato, T., Sato, A., Egawa, S., Ikeuchi, T., Tanaka, H., Nakano, R., Tanaka, K., Hozumi, I., Inuzuka, T., Takahashi, H., Tsuji, S. (1998). Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch. Nat Genet, 18, 111-117.
82. Lesort, M., Lee, M., Tucholski, J., Johnson, G.V. (2003). Cystamine inhibits caspase activity. Implications for the treatment of polyglutamine disorders. J Biol Chem, 278, 3825-3830.
83. Wei, H., Qin, Z.H., Senatorov, V.V., Wei, W., Wang, Y., Qian, Y., Chuang, D.M. (2001). Lithium suppresses excitotoxicity-induced striatal lesions in a rat model of Huntington's disease. Neurosci, 106, 603-612.
84. Carmichael, J., Sugars, K.L., Bao, Y.P., Rubinsztein, D.C. (2002). Glycogen synthase kinase-3beta inhibitors prevent cellular polyglutamine toxicity caused by the Huntington's disease mutation. J Biol Chem, 277, 33791-33798.
85. Wood, N.I., Morton, A.J. (2003). Chronic lithium chloride treatment has variable effects on motor behaviour and survival of mice transgenic for the Huntington's disease mutation. Brain Res Bull, 61, 375-383.
86. Gu, M., Gash, M.T., Mann, V.M., Javoy-Agid, F., Cooper, J.M., Schapira, A.H. (1996). Mitochondrial defect in Huntington's disease caudate nucleus. Ann Neurol, 39, 385-389.
87. Browne, S.E., Bowling, A.C., MacGarvey, U., Baik, M.J., Berger, S.C., Muqit, M.M., Bird, E.D., Beal, M.F. (1997). Oxidative damage and metabolic dysfunction in Huntington's disease, selective vulnerability of the basal ganglia. Ann Neurol, 41, 646-653.
88. Ferrante, R.J., Andreassen, O.A., Jenkins, B.G., Dedeoglu, A., Kuemmerle, S., Kubilus, J.K., Kaddurah-Daouk, R., Hersch, S.M., Beal, M.F. (2000). Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J Neurosci, 20, 4389-4397.
89. Dedeoglu, A., Kubilus, J.K., Yang, L., Ferrante, K.L., Hersch, S.M., Beal, M.F., Ferrante, R.J. (2003). Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J Neurochem, 85, 1359-1367.
90. Schmidt, B.J., Greenberg, C.R., Allingham-Hawkins, D.J., Spriggs, E.L. (2002). Expression of X-linked bulbospinal muscular atrophy (Kennedy disease) in two homozygous women. Neurology, 59, 770-772.
91. Katsuno, M., Adachi, H., Kume, A., Li, M., Nakagomi, Y., Niwa, H., Sang, C., Kobayashi, Y., Doyu, M., Sobue, G. (2002). Testosterone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Neuron, 35, 843-854.
92. Chevalier-Larsen, E.S., O'Brien, C.J., Wang, H., Jenkins, S.C., Holder, L., Lieberman, A.P., Merry, D.E. (2004). Castration restores function and neurofilament alterations of aged symptomatic males in a transgenic mouse model of spinal and bulbar muscular atrophy. J Neurosci, 24, 4778-4786.
93. Katsuno, M., Adachi, H., Doyu, M., Minamiyama, M., Sang, C., Kobayashi, Y., Inukai, A., Sobue, G. (2003). Leuprorelin rescues polyglutamine-dependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophy. Nat Med, 9, 768-773.
94. Banno, H., Katsuno, M., Suzuki, K., Takeuchi, Y., Kawashima, M., Suga, N., Takamori, M., Ito, M., Nakamura, T., Matsuo, K., Yamada, S., Oki, Y., Adachi, H., Minamiyama, M., Waza, M., Atsuta, N., Watanabe, H., Fujimoto, Y., Nakashima, T., Tanaka, F., Doyu, M., Sobue, G. (2009). Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy. Annual Neurology, 65, 140-150.
95. Yang, Z., Chang, Y.J., Yu, I.C., Yeh, S., Wu, C.C., Miyamoto, H., Merry, D.E., Sobue, G., Chen, L.M., Chang, S.S., Chang, C. (2007). ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor. Nat Med, 13, 348-353.
96. Watase, K., Gatchel, J.R., Sun, Y., Emamian, E., Atkinson, R., Richman, R., Mizusawa, H., Orr, H.T., Shaw, C., Zoghbi, H.Y. (2007). Lithium therapy improves neurological function and hippocampal dendritic arborization in a spinocerebellar ataxia type 1 mouse model. PLoS Med, 4, e182.