Pharmacological protein targets in polyglutamine diseases: Mutant polypeptides and their interactors

FEBS Letters

Volumn 587, Issue 13, 2013, Pages 1997-2007

  Margulis, Boris A ^a   Vigont, Vladimir ^a   Lazarev, Vladimir F ^a   Kaznacheyeva, Elena V ^a   Guzhova, Irina V ^a  

^a INSTITUTE OF CYTOLOGY   (Russian Federation)

Author keywords

Neurodegeneration Polyglutamine disease Polypeptide Protein conformation Drug target

Indexed keywords

ANDROGEN RECEPTOR; ATAXIN; HUNTINGTIN; MUTANT PROTEIN; NUCLEIC ACID BINDING PROTEIN; POLYGLUTAMINE; UNCLASSIFIED DRUG;

BRAIN ATROPHY; BRAIN DISEASE; BRAIN NERVE CELL; CYTOTOXICITY; DRUG TARGETING; GENE MUTATION; HUMAN; METABOLIC DISORDER; NONHUMAN; OLIGOMERIZATION; POLYGLUTAMINE DISEASE; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN SYNTHESIS; REVIEW;

ANIMALS; HUMANS; HUNTINGTON DISEASE; MOLECULAR TARGETED THERAPY; MUSCULAR DISORDERS, ATROPHIC; PEPTIDES; PROTEIN FOLDING; PROTEIN MULTIMERIZATION; PROTEOSTASIS DEFICIENCIES; SPINOCEREBELLAR ATAXIAS;

EID: 84878926416     PISSN: 00145793     EISSN: 18733468     Source Type: Journal    
DOI: 10.1016/j.febslet.2013.05.022     Document Type: Review

References (138)

1. C. Zuccato, M. Valenza, and E. Cattaneo Molecular mechanisms and potential therapeutical targets in Huntington's disease Physiol. Rev. 90 3 2010 905 981
2. G. Orozco Diaz, A. Nodarse Fleites, R. Cordovés Sagaz, and G. Auburger Autosomal dominant cerebellar ataxia: clinical analysis of 263 patients from a homogeneous population in Holguín, Cuba Neurology 40 9 1990 1369 1375
3. I. Silveira, P. Coutinho, P. Maciel, C. Gaspar, S. Hayes, A. Dias, J. Guimarães, L. Loureiro, J. Sequeiros, and G.A. Rouleau Analysis of SCA1, DRPLA, MJD, SCA2, and SCA6 CAG repeats in 48 Portuguese ataxia families Am. J. Med. Genet. 81 2 1998 134 138
4. M.U. Manto The wide spectrum of spinocerebellar ataxias (SCAs) Cerebellum 4 1 2005 2 6
5. M. Figiel, W.J. Szlachcic, P.M. Switonski, A. Gabka, and W.J. Krzyzosiak Mouse models of polyglutamine diseases: review and data table Mol. Neurobiol. 46 2 2012 393 429
6. F. Persichetti, J. Srinidhi, L. Kanaley, P. Ge, R.H. Myers, K. D'Arrigo, G.T. Barnes, M.E. MacDonald, J.P. Vonsattel, J.F. Gusella, and E.D. Bird Huntington's disease CAG trinucleotide repeats in pathologically confirmed post-mortem brains Neurobiol. Dis. 1 3 1994 159 166
7. J.W. Bradford, S. Li, and X.J. Li Polyglutamine toxicity in non-neuronal cells Cell Res. 20 4 2010 400 407
8. Li, J.Y. and Conforti, L. (2010) Axonopathy in Huntington's disease. Exp. Neurol. pii: S0014-4886(12)00319-6. doi: 10.1016. (Epub ahead of print).
9. P. Harjes, and E.E. Wanker The hunt for huntingtin function: interaction partners tell many different stories Trends Biochem. Sci. 28 8 2003 425 433
10. M. DiFiglia, E. Sapp, K. Chase, C. Schwarz, A. Meloni, C. Young, E. Martin, J.P. Vonsattel, R. Carraway, and S.A. Reeves Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons Neuron 14 5 1995 1075 1081
11. E.E. Wanker, C. Rovira, E. Scherzinger, R. Hasenbank, S. Wälter, D. Tait, J. Colicelli, and H. Lehrach HIP-I: a huntingtin interacting protein isolated by the yeast. Two-hybrid system Hum. Mol. Genet. 6 3 1997 487 495
12. E. Brusse, J.A. Maat-Kievit, and J.C. van Swieten Diagnosis and management of early- and late-onset cerebellar ataxia Clin. Genet. 71 1 2007 12 24
13. Klockgether, T. Ataxias. In: Goetz C.H. (Ed.). Textbook of Clinical Neurology. WB Saunders Publishing. Philadelphia.(2003) pp. 741-757.
14. H. Paulson, and Z. Ammache Ataxia and hereditary disorders Neurol. Clin. 19 3 2001 759 782
15. Rüb, U., Schöls, L., Paulson, H., Auburger, G., Kermer, P., Jen, J.C., Seidel, K., Korf, H.W. and Deller, T. (2013) Clinical features, neurogenetics and neuropathology of the polyglutamine spinocerebellar ataxias type 1, 2, 3, 6 and 7. Prog. Neurobiol. pii: S0301-0082(13)00010-5. doi: 10.1016. (Epub ahead of print).
16. H. Naito, and S. Oyanagi Familial myoclonus epilepsy and choreoathetosis: hereditary dentatorubral-pallidoluysian atrophy Neurology 32 8 1982 798 807
17. K. Suzuki, J. Zhou, T. Sato, K. Takao, T. Miyagawa, M. Oyake, M. Yamada, H. Takahashi, Y. Takahashi, J. Goto, and S. Tsuji DRPLA transgenic mouse substrains carrying single copy of full-length mutant human DRPLA gene with variable sizes of expanded CAG repeats exhibit CAG repeat length- and age-dependent changes in behavioralabnormalities and gene expression profiles Neurobiol. Dis. 46 2 2012 336 350
18. F. Tanaka, M. Katsuno, H. Banno, K. Suzuki, H. Adachi, and G. Sobue Current status of treatment of spinal and bulbar muscular atrophy Neural Plast. 2012 2012 369284
19. R.M. Cowin, A. Roscic, N. Bui, D. Graham, P. Paganetti, J.L. Jankowsky, A. Weiss, and R. Paylor Neuronal aggregates are associated with phenotypic onset in the R6/2 Huntington's disease transgenic mouse Behav. Brain Res. 229 2 2012 308 319
20. U. Simanainen, M. Brogley, Y.R. Gao, M. Jimenez, D.T. Harwood, D.J. Handelsman, and D.M. Robins Length of the human androgen receptor glutamine tract determines androgensensitivity in vivo Mol. Cell. Endocrinol. 342 1-2 2011 81 86
21. X. Lin, B. Antalffy, D. Kang, H.T. Orr, and H.Y. Zoghbi Polyglutamine expansion down-regulates specific neuronal genes before pathologic changes in SCA1 Nat. Neurosci. 3 2 2000 157 163
22. G. Oz, C.D. Nelson, D.M. Koski, P.G. Henry, M. Marjanska, D.K. Deelchand, R. Shanley, L.E. Eberly, H.T. Orr, and H.B. Clark Noninvasive detection of presymptomatic and progressive neurodegeneration in a mouse model of spinocerebellar ataxiatype 1 J. Neurosci. 30 10 2010 3831 3838
23. J.K. White, W. Auerbach, M.P. Duyao, J.P. Vonsattel, J.F. Gusella, A.L. Joyner, and M.E. MacDonald Huntingtin is required forneurogenesis and is not impaired by the Huntington's disease CAG expansion Nat. Genet. 17 4 1997 404 441
24. V.C. Wheeler, W. Auerbach, J.K. White, J. Srinidhi, A. Auerbach, A. Ryan, M.P. Duyao, V. Vrbanac, M. Weaver, J.F. Gusella, A.L. Joyner, and M.E. MacDonald Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse Hum. Mol. Genet. 8 1 1999 115 122
25. I.H. Park, N. Arora, H. Huo, N. Maherali, T. Ahfeldt, A. Shimamura, M.W. Lensch, C. Cowan, K. Hochedlinger, and G.Q. Daley Disease-specific induced pluripotent stem cells J. Cell Biol. 134 5 2008 877 886
26. S. Camnasio, A. Delli Carri, A. Lombardo, I. Grad, C. Mariotti, A. Castucci, B. Rozell, P. Lo Riso, V. Castiglioni, C. Zuccato, C. Rochon, Y. Takashima, G. Diaferia, I. Biunno, C. Gellera, M. Jaconi, A. Smith, O. Hovatta, L. Naldini, S. Di Donato, A. Feki, and E. Cattaneo The first reported generation of several induced pluripotent stem cell lines from homozygous and heterozygous Huntington's disease patients demonstrates mutation related enhanced lysosomal activity Neurobiol. Dis. 46 1 2012 41 51
27. Xia, G., Santostefano, K., Hamazaki, T., Liu, J., Subramony, S.H., Terada, N. and Ashizawa, T. (2012) Generation of human-induced pluripotent stem cells to model spinocerebellar ataxia type 2 in vitro. J. Mol. Neurosci. (Epub ahead of print).
28. V. Castiglioni, M. Onorati, C. Rochon, and E. Cattaneo Induced pluripotent stem cell lines from Huntington's disease mice undergo neuronal differetiation while showing alterations in the lysosomal pathway Neurobiol. Dis. 46 1 2012 30 40
29. G. Ossato, M.A. Digman, C. Aiken, T. Lukacsovich, J.L. Marsh, and E. Gratton A two-step path to inclusion formation of huntingtin peptides revealed by number and brightness analysis Biophys. J. 98 12 2010 3078 3085
30. P.H. Ren, J.E. Lauckner, I. Kachirskaia, J.E. Heuser, R. Melki, and R.R. Kopito Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates Nat. Cell Biol. 11 2 2009 219 225
31. G. Cisbani, and F. Cicchetti An in vitro perspective on the molecular mechanisms underlying mutant huntingtin protein toxicity Cell Death Dis. 3 2012 e382
32. M. Metzler, V. Legendre-Guillemin, L. Gan, V. Chopra, A. Kwok, P.S. McPherson, and M.R. Hayden HIP1 functions in clathrin-mediated endocytosis through binding to clathrinand adaptor protein 2 J. Biol. Chem. 276 42 2001 39271 39276
33. Y. Takeshita, R. Fujinaga, K. Kokubu, M.N. Islam, M.R. Jahan, A. Yanai, A. Kakizuka, and K. Shinoda Interaction of ataxin-3 with huntingtin-associated protein 1 through Josephin domain Neuroreport 22 5 2011 232 238
34. F.G. Gervais, R. Singaraja, S. Xanthoudakis, C.A. Gutekunst, B.R. Leavitt, M. Metzler, A.S. Hackam, J. Tam, J.P. Vaillancourt, V. Houtzager, D.M. Rasper, S. Roy, M.R. Hayden, and D.W. Nicholson Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi Nat. Cell Biol. 4 2 2002 95 105
35. M. Giacomello, J.C. Oliveros, J.R. Naranjo, and E. Carafoli Neuronal Ca(2+) dyshomeostasis in Huntington disease Prion 7 1 2013 76 84
36. R. Luthi-Carter, A. Strand, N.L. Peters, S.M. Solano, Z.R. Hollingsworth, A.S. Menon, A.S. Frey, B.S. Spektor, E.B. Penney, G. Schilling, C.A. Ross, D.R. Borchelt, S.J. Tapscott, A.B. Young, J.H. Cha, and J.M. Olson Decreased expression of striatal signaling genes in a mouse model of Huntington's disease Hum. Mol. Genet. 9 9 2000 1259 1271
37. A. Kuhn, D.R. Goldstein, A. Hodges, A.D. Strand, T. Sengstag, C. Kooperberg, K. Becanovic, M.A. Pouladi, K. Sathasivam, J.H. Cha, A.J. Hannan, M.R. Hayden, B.R. Leavitt, S.B. Dunnett, R.J. Ferrante, R. Albin, P. Shelbourne, M. Delorenzi, S.J. Augood, R.L. Faull, J.M. Olson, G.P. Bates, L. Jones, and R. Luthi-Carter Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage Hum. Mol. Genet. 16 15 2007 1845 1861
38. J.Q. Wang, Q. Chen, X. Wang, Q.C. Wang, Y. Wang, H.P. Cheng, C. Guo, Q. Sun, Q. Chen, and T.S. Tang Dysregulation of mitochondrial calcium signaling and superoxide flashes cause mitochondrial genomic DNA damage in Huntington disease J. Biol. Chem. 288 5 2013 3070 3084
39. T.S. Tang, H. Tu, E.Y. Chan, A. Maximov, Z. Wang, C.L. Wellington, M.R. Hayden, and I. Bezprozvanny Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1 Neuron 39 2 2003 227 239
40. T.S. Tang, C. Guo, H. Wang, X. Chen, and I. Bezprozvanny Neuroprotective effects of inositol 1,4,5-trisphosphate receptor C-terminal fragment in a Huntington's disease mouse model J. Neurosci. 29 5 2009 1257 1266
41. P.O. Bauer, R. Hudec, S. Ozaki, M. Okuno, E. Ebisui, K. Mikoshiba, and N. Nukina Genetic ablation and chemical inhibition of IP3R1 reduce mutant huntingtin aggregation Biochem. Biophys. Res. Commun. 416 1-2 2011 13 17
42. M.M. Zeron, O. Hansson, N. Chen, C.L. Wellington, B.R. Leavitt, P. Brundin, M.R. Hayden, and L.A. Raymond Increased sensitivity to N-methyl-d-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease Neuron 33 6 2002 849 860
43. S.H. Kim, C.A. Thomas, V.M. André, D.M. Cummings, C. Cepeda, M.S. Levine, and M.E. Ehrlich Forebrain striatal-specific expression of mutant huntingtin protein in vivo induces cell-autonomous age-dependent alterations in sensitivity to excitotoxicity and mitochondrial function ASN Neuro. 3 3 2011 e00060
44. 2+ signaling and apoptosis of medium spiny neurons in Huntington's disease Proc. Natl. Acad. Sci. USA 102 7 2005 2602 2607
45. J. Shehadeh, H.B. Fernandes, M.M. Zeron Mullins, R.K. Graham, B.R. Leavitt, M.R. Hayden, and L.A. Raymond Striatal neuronal apoptosis is preferentially enhanced by NMDA receptor activation in YAC transgenic mouse model of Huntington disease Neurobiol. Dis. 21 2 2006 392 403
46. C.M. Gladding, M.D. Sepers, J. Xu, L.Y. Zhang, A.J. Milnerwood, P.J. Lombroso, and L.A. Raymond Calpain and STriatal-Enriched protein tyrosine phosphatase (STEP) activation contribute to extrasynaptic NMDA receptor localization in a Huntington's disease mouse model Hum. Mol. Genet. 21 17 2012 3739 3752
47. X. Wu, M. Li, W. Tang, Y. Zheng, J. Lian, L. Xu, and M. Ji Design, synthesis, and in vitro antitumor activity evaluation of novel 4-pyrrylamino quinazoline derivatives Chem. Biol. Drug Des. 78 6 2011 932 940
48. A.V. Panov, C.A. Gutekunst, B.R. Leavitt, M.R. Hayden, J.R. Burke, W.J. Strittmatter, and J.T. Greenamyre Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines Nat. Neurosci. 5 8 2002 731 736
49. A. Rasola, M. Sciacovelli, B. Pantic, and P. Bernardi Signal transduction to the permeability transition pore FEBS Lett. 584 10 2010 1989 1996
50. X. Wang, S. Zhu, Z. Pei, M. Drozda, I.G. Stavrovskaya, S.J. Del Signore, K. Cormier, E.M. Shimony, H. Wang, R.J. Ferrante, B.S. Kristal, and R.M. Friedlander Inhibitors of cytochrome c release with therapeutic potential for Huntington's disease J. Neurosci. 28 38 2008 9473 9485
51. J. Fu, J. Jin, R.H. Cichewicz, S.A. Hageman, T.K. Ellis, L. Xiang, Q. Peng, M. Jiang, N. Arbez, K. Hotaling, C.A. Ross, and W. Duan Trans-(-)-ε-viniferin increases mitochondrial sirtuin 3 (SIRT3), activates AMP-activated protein kinase (AMPK), and protects cells in models of Huntington disease J. Biol. Chem. 287 29 2012 24460 24472
52. J. Carmichael, K.L. Sugars, Y.P. Bao, and D.C. Rubinsztein Glycogen synthase kinase-3beta inhibitors prevent cellular polyglutamine toxicity caused by the Huntington's disease mutation J. Biol. Chem. 277 37 2002 33791 33798
53. A. Valencia, P.B. Reeves, E. Sapp, X. Li, J. Alexander, K.B. Kegel, K. Chase, N. Aronin, and M. DiFiglia Mutant huntingtin and glycogen synthase kinase 3-beta accumulate in neuronal lipid rafts of a presymptomatic knock-in mouse model of Huntington's disease J. Neurosci. Res. 88 1 2010 179 190
54. J. Legleiter, G.P. Lotz, J. Miller, J. Ko, C. Ng, G.L. Williams, S. Finkbeiner, P.H. Patterson, and P.J. Muchowski Monoclonal antibodies recognize distinct conformational epitopes formed by polyglutamine in a mutant huntingtin fragment J. Biol. Chem. 284 32 2009 21647 21658
55. C.L. Wellington, L.M. Ellerby, C.A. Gutekunst, D. Rogers, S. Warby, R.K. Graham, O. Loubser, J. van Raamsdonk, R. Singaraja, Y.Z. Yang, J. Gafni, D. Bredesen, S.M. Hersch, B.R. Leavitt, S. Roy, D.W. Nicholson, and M.R. Hayden Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease J. Neurosci. 22 18 2002 7862 7872
56. S.J. Berke, F.A. Schmied, E.R. Brunt, L.M. Ellerby, and H.L. Paulson Caspase-mediated proteolysis of the polyglutamine disease protein ataxin-3 J. Neurochem. 89 4 2004 908 918
57. J.E. Young, L. Gouw, S. Propp, B.L. Sopher, J. Taylor, A. Lin, E. Hermel, A. Logvinova, S.F. Chen, S. Chen, D.E. Bredesen, R. Truant, L.J. Ptacek, A.R. La Spada, and L.M. Ellerby Proteolytic cleavage of ataxin-7 by caspase-7 modulates cellular toxicity and transcriptional dysregulation J. Biol. Chem. 282 41 2007 30150 30160
58. J. Gafni, E. Hermel, J.E. Young, C.L. Wellington, M.R. Hayden, and L.M. Ellerby Inhibition of calpain cleavage of huntingtin reduces toxicity: accumulation of calpain/caspase fragments in the nucleus J. Biol. Chem. 279 19 2004 20211 20220
59. J. Hübener, J.J. Weber, C. Richter, L. Honold, A. Weiss, F. Murad, P. Breuer, U. Wüllner, P. Bellstedt, F. Paquet-Durand, J. Takano, T.C. Saido, O. Riess, and H.P. Nguyen Calpain-mediated ataxin-3 cleavage in the molecular pathogenesis of spinocerebellar ataxia type 3 (SCA3) Hum. Mol. Genet. 22 3 2013 508 518
60. M.A. Poirier, H. Li, J. Macosko, S. Cai, M. Amzel, and C.A. Ross Huntingtin spheroids andprotofibrils as precursors in polyglutamine fibrilization J. Biol. Chem. 277 43 2002 41032 41037
61. I. Sánchez, C. Mahlke, and J. Yuan Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders Nature 421 6921 2003 373 379
62. M.F. Perutz, T. Johnson, M. Suzuki, and J.T. Finch Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases Proc. Natl. Acad. Sci. USA 91 12 1994 5355 5358
63. M.F. Perutz, J.T. Finch, J. Berriman, and A. Lesk Amyloid fibers are water-filled nanotubes Proc. Natl. Acad. Sci. USA 99 8 2002 5591 5595
64. C.A. Ross, and S.J. Tabrisi Huntington's disease: from molecular pathogenesis to clinical treatment Lancet Neurol. 10 1 2011 83 98
65. V. Gentile, C. Sepe, M. Calvani, M.A. Melone, R. Cotrufo, A.J. Cooper, J.P. Blass, and G. Peluso Tissue transglutaminase-catalyzed formation of high molecular-weight aggregates in vitro is favored with long polyglutamine domains: a possible mechanism contributing to CAG-triplet diseases Arch. Biochem. Biophys. 352 2 1998 314 321
66. V. Violante, A. Luongo, I. Pepe, S. Annunziata, and V. Gentile Transglutaminase-dependent formation of protein aggregates as possible biochemical mechanism for polyglutamine diseases Brain Res. Bull. 56 3-4 2001 169 172
67. G. Amantea, M. Cammarano, L. Zefferino, A. Martin, G. Romito, M. Piccirillo, and V. Gentile Molecular mechanisms responsible for the involvement of tissue transglutaminase in human diseases: Celiac disease Front. Biosci. 11 2006 249 255
68. M.V. Karpuj, M.W. Becher, J.E. Springer, D. Chabas, S. Youssef, R. Pedotti, D. Mitchell, and L. Steinman Prolonged survival and decreased abnormal movements in transgenic model of Huntington disease, with administration of the transglutaminase inhibitor cystamine Nat. Med. 8 2 2002 143 149
69. V. Tarlac, and E. Storey Role of proteolysis in polyglutamine disorders J. Neurosci. Res. 74 3 2003 406 416
70. S.F. Bortvedt, J.A. McLear, A. Messer, A.J. Ahern-Rindell, and W.J. Wolfgang Cystamine and intrabody co-treatment confers additional benefits in a fly model of Huntington's disease Neurobiol. Dis. 40 1 2010 130 134
71. S. Orru, M. Ruoppolo, S. Francese, L. Vitagliano, G. Marino, and C. Esposito Identification of tissue transglutaminase-reactive lysine residues in glyceraldehyde-3-phosphate dehydrogenase Protein Sci. 11 1 2002 137 146
72. M. Ruoppolo, S. Orrù, S. Francese, I. Caputo, and C. Esposito Structural characterization of transglutaminase-catalyzed cross-linking between glyceraldehyde 3-phosphate dehydrogenase and polyglutamine repeats Protein Sci. 12 1 2003 170 179
73. M.D. Berry Glyceraldehyde-3-phosphate dehydrogenase as a target for small-molecule disease-modifying therapies in human neurodegenerative disorders J. Psychiatry Neurosci. 29 5 2004 337 345
74. M. Barinaga An intriguing new lead on Huntington's disease Science 271 5253 1996 1233 1234
75. B. Koshy, T. Matilla, E.N. Burright, D.E. Merry, K.H. Fischbeck, H.T. Orr, and H.Y. Zoghbi Spinocerebellar ataxia type-1 and spinobulbar muscular atrophy gene products interact with glyceraldehyde-3-phosphate dehydrogenase Hum. Mol. Genet. 5 9 1996 1311 1318
76. J. Wu, F. Lin, and Z. Qin Sequestration of glyceraldehyde-3-phosphate dehydrogenase to aggregates formed by mutant huntingtin Acta Biochim. Biophys. Sin. (Shanghai) 39 11 2007 885 890
77. I.V. Guzhova, V.F. Lazarev, A.V. Kaznacheeva, M.V. Ippolitova, V.I. Muronetz, A.V. Kinev, and B.A. Margulis Novel mechanism of Hsp70 chaperone-mediated prevention of polyglutamine aggregates in a cellular model of huntington disease Hum. Mol. Genet. 20 20 2011 3953 3963
78. V.F. Lazarev, D.V. Sverchinskyi, M.V. Ippolitova, A.V. Kaznacheeva, I.V. Guzhova, and B.A. Margulis Factors affecting aggregate un cell models of Huntington disease and amyotrophic lateral sclerosis Acta Nat. 5 2 2013 83 92
79. J.S. Steffan, A. Kazantsev, O. Spasic-Boskovic, M. Greenwald, Y.Z. Zhu, H. Gohler, E.E. Wanker, G.P. Bates, D.E. Housman, and L.M. Thompson The Huntington's disease proteininteracts with p53 and CREB-binding protein and represses transcription Proc. Natl. Acad. Sci. USA 97 12 2000 6763 6768
80. L. Bodai, J. Pallos, L.M. Thompson, and J.L. Marsh Pcaf modulates polyglutamine pathology in a Drosophila model of Huntington's disease Neurodegener. Dis. 9 2 2012 104 106
81. J.S. Steffan, L. Bodai, J. Pallos, M. Poelman, A. McCampbell, B.L. Apostol, A. Kazantsev, E. Schmidt, Y.Z. Zhu, M. Greenwald, R. Kurokawa, D.E. Housman, G.R. Jackson, J.L. Marsh, and L.M. Thompson Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila Nature 413 6857 2001 739 743
82. A. Giralt, M. Puigdellívol, O. Carretón, P. Paoletti, J. Valero, A. Parra-Damas, C.A. Saura, J. Alberch, and S. Ginés Long-term memory deficits in Huntington's disease are associated with reduced CBP histone acetylase activity Hum. Mol. Genet. 21 6 2012 1203 1216
83. H.L. Montie, R.G. Pestell, and D.E. Merry SIRT1 modulates aggregation and toxicity through deacetylation of the androgen receptor in cell models of SBMA J. Neurosci. 31 48 2011 17425 17436
84. A. Johri, and M.F. Beal Huntington for new proteases: MMPs as the new target? Neuron 67 2 2010 171 173
85. Z. Zheng, A. Li, B.B. Holmes, J.C. Marasa, and M.I. Diamond An N-terminal nuclear export signal regulates trafficking and aggregation ofHuntingtin (Htt) protein exon 1 J. Biol. Chem. 288 9 2013 6063 6071
86. B. Huang, J. Schiefer, C. Sass, C.M. Kosinski, and S. Kochanek Inducing huntingtin inclusionformation in primary neuronal cell culture and in vivo by high-capacity adenoviral vectors expressing truncated and full-length huntingtin with polyglutamine expansion J. Gene Med. 10 3 2008 269 279
87. B.I. Bae, M.R. Hara, M.B. Cascio, C.L. Wellington, M.R. Hayden, C.A. Ross, H.C. Ha, X.J. Li, S.H. Snyder, and A. Sawa Mutant huntingtin: nuclear translocation and cytotoxicity mediated by GAPDH Proc. Natl. Acad. Sci. USA 103 9 2006 3405 3409
88. M. Hogel, R.B. Laprairie, and E.M. Denovan-Wright Promoters are differentially sensitive to N-terminal mutant huntingtin-mediated transcriptional repression PLoS One 7 7 2012 e41152
89. S.D. McCullough, X. Xu, S.Y. Dent, S. Bekiranov, R.G. Roeder, and P.A. Grant Reelin is a target of polyglutamine expanded ataxin-7 in human spinocerebellar ataxia type 7 (SCA7) astrocytes Proc. Natl. Acad. Sci. USA 109 52 2012 21319 21324
90. H. Xiao, Z. Yu, Y. Wu, J. Nan, D.E. Merry, J.M. Sekiguchi, D.O. Ferguson, A.P. Lieberman, and G.R. Dressler A polyglutamine expansion disease protein sequesters PTIP to attenuate DNA repair and increase genomic instability Hum. Mol. Genet. 21 19 2012 4225 4236
91. J.A. Olzmann, L. Li, and L.S. Chin Aggresome formation and neurodegenerative diseases: therapeutic implications Curr. Med. Chem. 15 1 2008 47 60
92. J.P. Taylor, F. Tanaka, J. Robitschek, C.M. Sandoval, A. Taye, S. Markovic-Plese, and K.H. Fischbeck Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein Hum. Mol. Genet. 12 7 2003 749 757
93. Y. Wang, A.B. Meriin, N. Zaarur, N.V. Romanova, Y.O. Chernoff, C.E. Costello, and M.Y. Sherman Abnormal proteins can form aggresome in yeast: aggresome-targeting signals and components of the machinery FASEB J. 23 2 2009 451 463
94. S.V. Todi, K.M. Scaglione, J.R. Blount, V. Basrur, K.P. Conlon, A. Pastore, K. Elenitoba-Johnson, and H.L. Paulson Activity and cellular functions of the deubiquitinating enzyme and polyglutamine disease protein ataxin-3 are regulated by ubiquitination at lysine 117 J. Biol. Chem. 285 50 2010 39303 39313
95. B.B. Holmes, and M.I. Diamond Cellular mechanisms of protein aggregate propagation Curr. Opin. Neurol. 25 6 2012 721 726
96. R.S. Trevino, J.E. Lauckner, Y. Sourigues, M.M. Pearce, L. Bousset, R. Melki, and R.R. Kopito Fibrillar structure and charge determine the interaction of polyglutamine protein aggregates with the cell surface J. Biol. Chem. 287 35 2012 29722 29728
97. E.A. Kikis, T. Gidalevitz, and R.I. Morimoto Protein homeostasis in models of aging and age-related conformational disease Adv. Exp. Med. Biol. 694 2010 138 159
98. N.R. Jana, E.A. Zemskov, Gh. Wang, and N. Nukina Altered proteasomal function due to the expression of polyglutamine-expanded truncated N-terminal huntingtin induces apoptosis by caspase activation through mitochondrial cytochrome c release Hum. Mol. Genet. 10 10 2001 1049 1059
99. D.L. Stenoien, M. Mielke, and M.A. Mancini Intranuclear ataxin1 inclusions contain both fast- and slow-exchanging components Nat. Cell Biol. 4 10 2002 806 810
100. Y. Park, S. Hong, S.J. Kim, and S. Kang Proteasome function is inhibited by polyglutamine-expanded ataxin-1, the SCA1 gene product Mol. Cell 19 1 2005 23 30
101. C.J. Maynard, C. Böttcher, Z. Ortega, R. Smith, B.I. Florea, M. Díaz-Hernández, P. Brundin, H.S. Overkleeft, J.Y. Li, J.J. Lucas, and N.P. Dantuma Accumulation of ubiquitin conjugates in a polyglutamine disease model occurs without global ubiquitin/proteasome system impairment Proc. Natl. Acad. Sci. USA 106 33 2009 13986 13991
102. Z. Ortega, M. Díaz-Hernández, C.J. Maynard, F. Hernández, N.P. Dantuma, and J.J. Lucas Acute polyglutamine expression in inducible mouse model unravels ubiquitin/proteasome system impairment and permanent recovery attributable to aggregate formation J. Neurosci. 30 10 2010 3675 3688
103. M.S. Hipp, C.N. Patel, K. Bersuker, B.E. Riley, S.E. Kaiser, T.A. Shaler, M. Brandeis, and R.R. Kopito Indirect inhibition of 26S proteasome activity in a cellular model of Huntington's disease J. Cell Biol. 196 5 2012 573 587
104. S. Subramaniam, K.M. Sixt, R. Barrow, and S.H. Snyder Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity Science 324 5932 2009 1327 1330
105. A. Janer, A. Werner, J. Takahashi-Fujigasaki, A. Daret, H. Fujigasaki, K. Takada, C. Duyckaerts, A. Brice, A. Dejean, and A. Sittler SUMOylation attenuates the aggregation propensity and cellular toxicity of the polyglutamine expanded ataxin-7 Hum. Mol. Genet. 19 1 2010 181 195
106. Z.Z. Chong, Y.C. Shang, S. Wang, and K. Maiese Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin Prog. Neurobiol. 99 2 2012 128 148
107. B. Ravikumar, C. Vacher, Z. Berger, J.E. Davies, S. Luo, L.G. Oroz, F. Scaravilli, D.F. Easton, R. Duden, C.J. O'Kane, and D.C. Rubinsztein Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease Nat. Genet. 36 6 2004 585 595
108. A. Roscic, B. Baldo, C. Crochemore, D. Marcellin, and P. Paganetti Induction of autophagy with catalytic mTOR inhibitors reduces huntingtin aggregates in a neuronal cell model J. Neurochem. 119 2 2011 398 407
109. S. Sarkar, E.O. Perlstein, S. Imarisio, S. Pineau, A. Cordenier, R.L. Maglathlin, J.A. Webster, T.A. Lewis, C.J. O'Kane, S.L. Schreiber, and D.C. Rubinsztein Small molecules enhance autophagy and reduce toxicity in Huntington's disease models Nat. Chem. Biol. 3 6 2007 331 338
110. S. Shoji-Kawata, R. Sumpter, M. Leveno, G.R. Campbell, Z. Zou, L. Kinch, A.D. Wilkins, Q. Sun, K. Pallauf, D. MacDuff, C. Huerta, H.W. Virgin, J.B. Helms, R. Eerland, S.A. Tooze, R. Xavier, D.J. Lenschow, A. Yamamoto, D. King, O. Lichtarge, N.V. Grishin, S.A. Spector, D.V. Kaloyanova, and B. Levine Identification of a candidate therapeutic autophagy-inducing peptide Nature 494 7436 2013 201 206
111. F.U. Hartl, and M. Hayer-Hartl Molecular chaperones in the cytosol: from nascent chain to folded protein Science 295 5561 2002 1852 1858
112. M. Akerfelt, R.I. Morimoto, and L. Sistonen Heat shock factors: integrators of cell stress, development and lifespan Nat. Rev. Mol. Cell. Biol. 11 8 2010 545 555
113. S.M. Chafekar, and M.L. Duennwald Impaired heat shock response in cells expressing full-length polyglutamine-expanded huntingtin PLoS One 7 5 2012 e37929
114. T.V. Novoselova, B.A. Margulis, S.S. Novoselov, A.M. Sapozhnikov, J. van der Spuy, M.E. Cheetham, and I.V. Guzhova Treatment with extracellular HSP70/HSC70 protein can reduce polyglutamine toxicity and aggregation J. Neurochem. 94 3 2005 597 606
115. S.Y. Shieh, and N.M. Bonini Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila Hum. Mol. Genet. 20 24 2011 4810 4821
116. O. Hansson, J. Nylandsted, R.F. Castilho, M. Leist, M. Jäättelä, and P. Brundin Overexpression of heat shock protein 70 in R6/2 Huntington's disease mice has only modest effects on disease progression Behav. Brain Res. 970 1-2 2003 47 57
117. H. Zhou, S.H. Li, and X.J. Li Chaperone suppression of cellular toxicity of huntingtin is independent of polyglutamine aggregation J. Biol. Chem. 276 51 2001 48417 48424
118. C.K. Bailey, I.F. Andriola, H.H. Kampinga, and D.E. Merry Molecular chaperones enhance the degradation of expanded polyglutamine repeat androgen receptor in a cellular model of spinal and bulbar muscular atrophy Hum. Mol. Genet. 11 5 2002 515 523
119. H.A. Popiel, T. Takeuchi, H. Fujita, K. Yamamoto, C. Ito, H. Yamane, S. Muramatsu, T. Toda, K. Wada, and Y. Nagai Hsp40 gene therapy exerts therapeutic effects on polyglutamine disease mice via anon-cell autonomous mechanism PLoS One 7 11 2012 e51069
120. J. Labbadia, S.S. Novoselov, J.S. Bett, A. Weiss, P. Paganetti, G.P. Bates, and M.E. Cheetham Suppression of protein aggregation by chaperone modification of high molecular weight complexes Brain 135 Pt 4 2012 1180 1196
121. T. Appl, L. Kaltenbach, D.C. Lo, and G.C. Terstappen Targeting mutant huntingtin for the development of disease-modifying therapy Drug Discovery Today 17 21-22 2012 1217 1223
122. R. Grondin, M.D. Kaytor, Y. Ai, P.T. Nelson, D.R. Thakker, J. Heisel, M.R. Weatherspoon, J.L. Blum, E.N. Burright, Z. Zhang, and W.F. Kaemmerer Six-month partial suppression of Huntingtin is well tolerated in the adult rhesus striatum Brain 135 Pt 4 2012 1197 1209
123. S.Q. Harper, P.D. Staber, X. He, S.L. Eliason, I.H. Martins, Q. Mao, L. Yang, R.M. Kotin, H.L. Paulson, and B.L. Davidson RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model Proc. Natl. Acad. Sci. USA 102 16 2005 5820 5825
124. E. Rodriguez-Lebron, E.M. Denovan-Wright, K. Nash, A.S. Lewin, and R.J. Mandel 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 4 2005 618 633
125. M. Garriga-Canut, C. Agustín-Pavón, F. Herrmann, A. Sánchez, M. Dierssen, C. Fillat, and M. Isalan Synthetic zinc finger repressors reduce mutant huntingtin expression in the brain of R6/2 mice Proc. Natl. Acad. Sci. USA 109 45 2012 e3136 e3145
126. E. Rockabrand, N. Slepko, A. Pantalone, V.N. Nukala, A. Kazantsev, J.L. March, P.G. Sullivan, J.S. Steffan, S.L. Sensi, and L.M. Thompson The first 17 amino acids of Huntingtin modulate its sub-cellular localization, aggregation and effects on calcium homeostasis Hum. Mol. Genet. 16 1 2007 61 77
127. D.C. Butler, and A. Messer Bifunctional anti-huntingtin proteasome-directed intrabodies mediate efficient degradation of mutant huntingtin exon 1 protein fragments PLoS One 6 12 2011 e29199
128. C. Soto, M.S. Kindy, M. Baumann, and B. Frangione Inhibition ofAlzheimer's amyloidosis by peptides that prevent β-sheet conformation Biochem. Biophys. Res. Commun. 226 3 1996 672 680
129. Y. Nagai, T. Tucker, H. Ren, D.J. Kenan, B.S. Henderson, J.D. Keene, W.J. Strittmatter, and J.R. Burke Inhibition of polyglutamine protein aggregation and cell death by novel peptides identified by phage display screening J. Biol. Chem. 275 14 2000 10437 10442
130. H.A. Popiel, Y. Nagai, N. Fujikake, and T. Toda Protein transduction domain-mediated delivery of QBP1 suppresses polyglutamine-induced neurodegeneration in vivo Mol. Ther. 15 2 2007 303 309
131. Y. Nagai, N. Fujikake, K. Ohno, H. Higashiyama, H.A. Popiel, J. Rahadian, M. Yamaguchi, W.J. Strittmatter, J.R. Burke, and T. Toda Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila Hum. Mol. Genet. 12 11 2003 1253 1259
132. H.A. Popiel, T. Takeuchi, H. Fujita, K. Yamamoto, C. Ito, H. Yamane, S. Muramatsu, T. Toda, K. Wada, and Y. Nagai Hsp40 gene therapy exerts therapeutic effects on polyglutamine disease mice via a non-cell autonomous mechanism PLoS One 7 11 2012 e51069
133. Popiel, H.A., Takeuchi, T., Burke, J.R., Strittmatter, W.J., Toda, T., Wada, K. and Nagai, Y. (2013) Inhibition of protein misfolding/aggregation using polyglutamine binding peptide QBP1 as a therapy for the polyglutamine siseases. Neurotherapeutics. http://dx.doi.org/10.1007/s13311-013-0184-7 (Epub ahead of print).
134. X. Chen, J. Wu, Y. Luo, X. Liang, C. Supnet, M.W. Kim, G.P. Lotz, G. Yang, P.J. Muchowski, T. Kodadek, and I. Bezprozvanny Expanded polyglutamine-binding peptoid as a novel therapeutic agent for treatment of Huntington's disease Nat. Chem. Biol. 18 9 2011 1113 1125
135. R.A. Fuentealba, J. Marasa, M.I. Diamond, D. Piwnica-Worms, and C.C. Weihl An aggregation sensing reporter identifies leflunomide and teriflunomide as polyglutamine aggregate inhibitors Hum. Mol. Genet. 21 3 2012 664 680
136. H. Zhang, N. Pan, S. Xiong, S. Zou, H. Li, L. Xiao, Z. Cao, A. Tunnacliffe, and Z. Huang Inhibition of polyglutamine-mediated proteotoxicity by Astragalus membranaceus polysaccharide through the DAF-16/FOXO transcription factor in Caenorhabditis elegans Biochem. J. 441 1 2012 417 424
137. R.K. Graham, Y. Deng, E.J. Slow, B. Haigh, N. Bissada, G. Lu, J. Pearson, J. Shehadeh, L. Bertram, Z. Murphy, S.C. Warby, C.N. Doty, S. Roy, C.L. Wellington, B.R. Leavitt, L.A. Raymond, D.W. Nicholson, and M.R. Hayden Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin J. Cell Biol. 125 6 2006 1179 1191
138. P. Haldimann, M. Muriset, L. Vígh, and P. Goloubinoff The novel hydroxylamine derivative NG-094 suppresses polyglutamine protein toxicity in Caenorhabditis elegans J. Biol. Chem. 286 21 2011 18784 18794