Neurotoxic effects of androgens in spinal and bulbar muscular atrophy

Frontiers in Neuroendocrinology

Volumn 32, Issue 4, 2011, Pages 416-425

  Parodi, Sara ^a   Pennuto, Maria ^b  

^a G GASLINI INSTITUTE   (Italy)

^b ISTITUTO ITALIANO DI TECNOLOGIA   (Italy)

Author keywords

Androgen receptor; Androgens; Motor neurons; Neurodegeneration; Polyglutamine diseases; Spinal and bulbar muscular atrophy

Indexed keywords

5 HYDROXY 1,7 BIS(3,4 DIMETHOXYPHENYL) 1,4,6 HEPTATRIEN 3 ONE; ALVESPIMYCIN; ANDROGEN; ANDROGEN RECEPTOR; ASC J 9; B 2; CHEMICAL COMPOUND; DUTASTERIDE; FLUTAMIDE; GELDANAMYCIN; LEUPRORELIN; MUTANT PROTEIN; PLACEBO; POLYGLUTAMINE; RAPAMYCIN; RTI 015B; RTI 016; RTI 051B; SELECTIVE ANDROGEN RECEPTOR MODULATOR; TANESPIMYCIN; TEPRENONE; TESTOSTERONE; UNCLASSIFIED DRUG;

BRAIN STEM; GENE; KENNEDY DISEASE; MOTONEURON; NERVE CELL DEGENERATION; NEUROMUSCULAR DISEASE; NEUROTOXICITY; NONHUMAN; NUCLEOTIDE SEQUENCE; PATHOGENESIS; PATHOGENICITY; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN STRUCTURE; RECEPTOR BINDING; REVIEW; SEX DIFFERENCE; SPINAL CORD;

ANDROGENS; ANIMALS; BULBO-SPINAL ATROPHY, X-LINKED; CYTOTOXINS; HUMANS; MALE; MODELS, BIOLOGICAL; NERVE DEGENERATION; NEURONS; RECEPTORS, ANDROGEN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 80053094971     PISSN: 00913022     EISSN: 18734596     Source Type: Journal    
DOI: 10.1016/j.yfrne.2011.06.003     Document Type: Review

References (119)

1. Adachi H., Katsuno M., Minamiyama M., Sang C., Pagoulatos G., Angelidis C., Kusakabe M., Yoshiki A., Kobayashi Y., Doyu M., Sobue G. 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. 2003, 23:2203-2211.
2. Adachi H., Katsuno M., Minamiyama M., Waza M., Sang C., Nakagomi Y., Kobayashi Y., Tanaka F., Doyu M., Inukai A., Yoshida M., Hashizume Y., Sobue G. Widespread nuclear and cytoplasmic accumulation of mutant androgen receptor in SBMA patients. Brain 2005, 128:659-670.
3. Adachi H., Waza M., Tokui K., Katsuno M., Minamiyama M., Tanaka F., Doyu M., Sobue G. CHIP overexpression reduces mutant androgen receptor protein and ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model. J. Neurosci. 2007, 27:5115-5126.
4. Arrasate M., Mitra S., Schweitzer E.S., Segal M.R., Finkbeiner S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 2004, 431:805-810.
5. 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. Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy. Ann. Neurol. 2009, 65:140-150.
6. Bauer P.O., Nukina N. The pathogenic mechanisms of polyglutamine diseases and current therapeutic strategies. J. Neurochem. 2009, 110:1737-1765.
7. Bhattacharyya A., Thakur A.K., Chellgren V.M., Thiagarajan G., Williams A.D., Chellgren B.W., Creamer T.P., Wetzel R. Oligoproline effects on polyglutamine conformation and aggregation. J. Mol. Biol. 2006, 355:524-535.
8. Bichelmeier U., Schmidt T., Hubener J., Boy J., Ruttiger L., Habig K., Poths S., Bonin M., Knipper M., Schmidt W.J., Wilbertz J., Wolburg H., Laccone F., Riess O. Nuclear localization of ataxin-3 is required for the manifestation of symptoms in SCA3: in vivo evidence. J. Neurosci. 2007, 27:7418-7428.
9. Bodner R.A., Outeiro T.F., Altmann S., Maxwell M.M., Cho S.H., Hyman B.T., McLean P.J., Young A.B., Housman D.E., Kazantsev A.G. Pharmacological promotion of inclusion formation: a therapeutic approach for Huntington's and Parkinson's diseases. Proc. Natl Acad. Sci. USA 2006, 103:4246-4251.
10. Chang C.S., Kokontis J., Liao S.T. Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science 1988, 240:324-326.
11. Chen H.K., Fernandez-Funez P., Acevedo S.F., Lam Y.C., Kaytor M.D., Fernandez M.H., Aitken A., Skoulakis E.M., Orr H.T., Botas J., Zoghbi H.Y. Interaction of Akt-phosphorylated ataxin-1 with 14-3-3 mediates neurodegeneration in spinocerebellar ataxia type 1. Cell 2003, 113:457-468.
12. Chevalier-Larsen E.S., O'Brien C.J., Wang H., Jenkins S.C., Holder L., Lieberman A.P., Merry D.E. Castration restores function and neurofilament alterations of aged symptomatic males in a transgenic mouse model of spinal and bulbar muscular atrophy. J. Neurosci. 2004, 24:4778-4786.
13. Crippa V., Carra S., Rusmini P., Sau D., Bolzoni E., Bendotti C., De Biasi S., Poletti A. A role of small heat shock protein B8 (HspB8) in the autophagic removal of misfolded proteins responsible for neurodegenerative diseases. Autophagy 2010, 6:958-960.
14. Crippa V., Sau D., Rusmini P., Boncoraglio A., Onesto E., Bolzoni E., Galbiati M., Fontana E., Marino M., Carra S., Bendotti C., De Biasi S., Poletti A. The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS). Hum. Mol. Genet. 2010, 19:3440-3456.
15. Cutress M.L., Whitaker H.C., Mills I.G., Stewart M., Neal D.E. Structural basis for the nuclear import of the human androgen receptor. J. Cell Sci. 2008, 121:957-968.
16. Darnell G., Orgel J.P., Pahl R., Meredith S.C. Flanking polyproline sequences inhibit beta-sheet structure in polyglutamine segments by inducing PPII-like helix structure. J. Mol. Biol. 2007, 374:688-704.
17. David G., Abbas N., Stevanin G., Durr A., Yvert G., Cancel G., Weber C., Imbert G., Saudou F., Antoniou E., Drabkin H., Gemmill R., Giunti P., Benomar A., Wood N., Ruberg M., Agid Y., Mandel J.L., Brice A. Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat. Genet. 1997, 17:65-70.
18. Dedhar S., Rennie P.S., Shago M., Hagesteijn C.Y., Yang H., Filmus J., Hawley R.G., Bruchovsky N., Cheng H., Matusik R.J., Giguere V. Inhibition of nuclear hormone receptor activity by calreticulin. Nature 1994, 367:480-483.
19. Dehay B., Bertolotti A. Critical role of the proline-rich region in Huntingtin for aggregation and cytotoxicity in yeast. J. Biol. Chem. 2006, 281:35608-35615.
20. Ding D., Xu L., Menon M., Reddy G.P., Barrack E.R. Effect of GGC (glycine) repeat length polymorphism in the human androgen receptor on androgen action. Prostate 2005, 62:133-139.
21. Dubbink H.J., Hersmus R., Verma C.S., van der Korput H.A., Berrevoets C.A., van Tol J., Ziel-van der Made A.C., Brinkmann A.O., Pike A.C., Trapman J. Distinct recognition modes of FXXLF and LXXLL motifs by the androgen receptor. Mol. Endocrinol. 2004, 18:2132-2150.
22. Duennwald M.L., Jagadish S., Muchowski P.J., Lindquist S. Flanking sequences profoundly alter polyglutamine toxicity in yeast. Proc. Natl Acad. Sci. USA 2006, 103:11045-11050.
23. Echaniz-Laguna A., Rousso E., Anheim M., Cossee M., Tranchant C. A family with early-onset and rapidly progressive X-linked spinal and bulbar muscular atrophy. Neurology 2005, 64:1458-1460.
24. Fernandez-Rhodes L.E., Kokkinis A.D., White M.J., Watts C.A., Auh S., Jeffries N.O., Shrader J.A., Lehky T.J., Li L., Ryder J.E., Levy E.W., Solomon B.I., Harris-Love M.O., La Pean A., Schindler A.B., Chen C., Di Prospero N.A., Fischbeck K.H. Efficacy and safety of dutasteride in patients with spinal and bulbar muscular atrophy: a randomised placebo-controlled trial. Lancet Neurol. 2011, 10:140-147.
25. Friedman M.J., Shah A.G., Fang Z.H., Ward E.G., Warren S.T., Li S., Li X.J. Polyglutamine domain modulates the TBP-TFIIB interaction: implications for its normal function and neurodegeneration. Nat. Neurosci. 2007, 10:1519-1528.
26. Fu M.H., Lan M.Y., Liu J.S., Lai S.L., Chen S.S., Chang Y.Y. Kennedy disease mimics amyotrophic lateral sclerosis: a case report. Acta Neurol. Taiwan 2008, 17:99-103.
27. Gao T., Marcelli M., McPhaul M.J. Transcriptional activation and transient expression of the human androgen receptor. J. Steroid Biochem. Mol. Biol. 1996, 59:9-20.
28. Giovannucci E., Stampfer M.J., Krithivas K., Brown M., Dahl D., Brufsky A., Talcott J., Hennekens C.H., Kantoff P.W. The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc. Natl Acad. Sci. USA 1997, 94:3320-3323.
29. Haelens A., Tanner T., Denayer S., Callewaert L., Claessens F. The hinge region regulates DNA binding, nuclear translocation, and transactivation of the androgen receptor. Cancer Res. 2007, 67:4514-4523.
30. Haller R.G., Wyrick P., Taivassalo T., Vissing J. Aerobic conditioning: an effective therapy in McArdle's disease. Ann. Neurol. 2006, 59:922-928.
31. Harada N., Mitani T., Higashimura Y., Yamaji R., Okamoto K., Nakano Y., Inui H. Involvement of three glutamine tracts in human androgen receptor transactivation. J. Steroid Biochem. Mol. Biol. 2010, 118:77-84.
32. He B., Bowen N.T., Minges J.T., Wilson E.M. Androgen-induced NH2- and COOH-terminal interaction inhibits p160 coactivator recruitment by activation function 2. J. Biol. Chem. 2001, 276:42293-42301.
33. He B., Kemppainen J.A., Voegel J.J., Gronemeyer H., Wilson E.M. Activation function 2 in the human androgen receptor ligand binding domain mediates interdomain communication with the NH(2)-terminal domain. J. Biol. Chem. 1999, 274:37219-37225.
34. He B., Kemppainen J.A., Wilson E.M. FXXLF and WXXLF sequences mediate the NH2-terminal interaction with the ligand binding domain of the androgen receptor. J. Biol. Chem. 2000, 275:22986-22994.
35. Helmlinger D., Tora L., Devys D. Transcriptional alterations and chromatin remodeling in polyglutamine diseases. Trends Genet. 2006, 22:562-570.
36. Hillmer A.M., Hanneken S., Ritzmann S., Becker T., Freudenberg J., Brockschmidt F.F., Flaquer A., Freudenberg-Hua Y., Jamra R.A., Metzen C., Heyn U., Schweiger N., Betz R.C., Blaumeiser B., Hampe J., Schreiber S., Schulze T.G., Hennies H.C., Schumacher J., Propping P., Ruzicka T., Cichon S., Wienker T.F., Kruse R., Nothen M.M. Genetic variation in the human androgen receptor gene is the major determinant of common early-onset androgenetic alopecia. Am. J. Hum. Genet. 2005, 77:140-148.
37. Howarth J.L., Kelly S., Keasey M.P., Glover C.P., Lee Y.B., Mitrophanous K., Chapple J.P., Gallo J.M., Cheetham M.E., Uney J.B. Hsp40 molecules that target to the ubiquitin-proteasome system decrease inclusion formation in models of polyglutamine disease. Mol. Ther. 2007, 15:1100-1105.
38. Hsing A.W., Gao Y.T., Wu G., Wang X., Deng J., Chen Y.L., Sesterhenn I.A., Mostofi F.K., Benichou J., Chang C. Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China. Cancer Res. 2000, 60:5111-5116.
39. Imbert G., Saudou F., Yvert G., Devys D., Trottier Y., Garnier J.M., Weber C., Mandel J.L., Cancel G., Abbas N., Durr A., Didierjean O., Stevanin G., Agid Y., Brice A. Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nat. Genet. 1996, 14:285-291.
40. Ishihara K., Yamagishi N., Saito Y., Adachi H., Kobayashi Y., Sobue G., Ohtsuka K., Hatayama T. Hsp105alpha suppresses the aggregation of truncated androgen receptor with expanded CAG repeats and cell toxicity. J. Biol. Chem. 2003, 278:25143-25150.
41. Jeppesen T.D., Schwartz M., Olsen D.B., Wibrand F., Krag T., Duno M., Hauerslev S., Vissing J. Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy. Brain 2006, 129:3402-3412.
42. Johansen J.A., Troxell-Smith S.M., Yu Z., Mo K., Monks D.A., Lieberman A.P., Breedlove S.M., Jordan C.L. Prenatal flutamide enhances survival in a myogenic mouse model of spinal bulbar muscular atrophy. Neurodegener. Dis. 2010.
43. Kaku N., Matsuda K., Tsujimura A., Kawata M. Characterization of nuclear import of the domain-specific androgen receptor in association with the importin alpha/beta and Ran-guanosine 5'-triphosphate systems. Endocrinology 2008, 149:3960-3969.
44. Katsuno M., Adachi H., Doyu M., Minamiyama M., Sang C., Kobayashi Y., Inukai A., Sobue G. Leuprorelin rescues polyglutamine-dependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophy. Nat. Med. 2003, 9:768-773.
45. Katsuno M., Adachi H., Kume A., Li M., Nakagomi Y., Niwa H., Sang C., Kobayashi Y., Doyu M., Sobue G. Testosterone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Neuron 2002, 35:843-854.
46. Katsuno M., Adachi H., Minamiyama M., Waza M., Doi H., Kondo N., Mizoguchi H., Nitta A., Yamada K., Banno H., Suzuki K., Tanaka F., Sobue G. Disrupted transforming growth factor-beta signaling in spinal and bulbar muscular atrophy. J. Neurosci. 2010, 30:5702-5712.
47. Katsuno M., Adachi H., Minamiyama M., Waza M., Tokui K., Banno H., Suzuki K., Onoda Y., Tanaka F., Doyu M., Sobue G. Reversible disruption of dynactin 1-mediated retrograde axonal transport in polyglutamine-induced motor neuron degeneration. J. Neurosci. 2006, 26:12106-12117.
48. Katsuno M., Banno H., Suzuki K., Takeuchi Y., Kawashima M., Yabe I., Sasaki H., Aoki M., Morita M., Nakano I., Kanai K., Ito S., Ishikawa K., Mizusawa H., Yamamoto T., Tsuji S., Hasegawa K., Shimohata T., Nishizawa M., Miyajima H., Kanda F., Watanabe Y., Nakashima K., Tsujino A., Yamashita T., Uchino M., Fujimoto Y., Tanaka F., Sobue G. Efficacy and safety of leuprorelin in patients with spinal and bulbar muscular atrophy (JASMITT study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010, 9:875-884.
49. Katsuno M., Sang C., Adachi H., Minamiyama M., Waza M., Tanaka F., Doyu M., Sobue G. Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron disease. Proc. Natl Acad. Sci. USA 2005, 102:16801-16806.
50. Kawaguchi Y., Okamoto T., Taniwaki M., Aizawa M., Inoue M., Katayama S., Kawakami H., Nakamura S., Nishimura M., Akiguchi I., Kimura J., Narumiya S., Kakizuka A. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat. Genet. 1994, 8:221-228.
51. Kawahara H. A family of progressive bulbar palsy. Aichi Med. J. 1897, 16:3-4.
52. Kennedy W.R., Alter M., Sung J.H. Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait. Neurology 1968, 18:671-680.
53. Klement I.A., Skinner P.J., Kaytor M.D., Yi H., Hersch S.M., Clark H.B., Zoghbi H.Y., Orr H.T. Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 1998, 95:41-53.
54. Koide R., Ikeuchi T., Onodera O., Tanaka H., Igarashi S., Endo K., Takahashi H., Kondo R., Ishikawa A., Hayashi T., Saito M., Tomoda A., Miike T., Naito H., Ikuta F., Tsuji S. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nat. Genet. 1994, 6:9-13.
55. La Spada A.R., Wilson E.M., Lubahn D.B., Harding A.E., Fischbeck K.H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 1991, 352:77-79.
56. Langley E., Kemppainen J.A., Wilson E.M. Intermolecular NH2-/carboxyl-terminal interactions in androgen receptor dimerization revealed by mutations that cause androgen insensitivity. J. Biol. Chem. 1998, 273:92-101.
57. Langley E., Zhou Z.X., Wilson E.M. Evidence for an anti-parallel orientation of the ligand-activated human androgen receptor dimer. J. Biol. Chem. 1995, 270:29983-29990.
58. Lieberman A.P., Harmison G., Strand A.D., Olson J.M., Fischbeck K.H. Altered transcriptional regulation in cells expressing the expanded polyglutamine androgen receptor. Hum. Mol. Genet. 2002, 11:1967-1976.
59. Lim J., Crespo-Barreto J., Jafar-Nejad P., Bowman A.B., Richman R., Hill D.E., Orr H.T., Zoghbi H.Y. Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1. Nature 2008, 452:713-718.
60. Lubahn D.B., Joseph D.R., Sullivan P.M., Willard H.F., French F.S., Wilson E.M. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 1988, 240:327-330.
61. Macdonald M.E., Ambrose C.M., Duyao M.P., Myers R.H., Lin C., Srinidhi L., Barnes G., Taylor S.A., James M., Groot N., Macfarlane H., Jenkins B., Anderson M.A., Wexler N.S., Gusella J.F., Bates G.P., Baxendale S., Hummerich H., Kirby S., North M., Youngman S., Mott R., Zehetner G., Sedlacek Z., Poustka A., Frischauf A.M., Lehrach H., Buckler A.J., Church D., Doucettestamm L., Odonovan M.C., Ribaramirez L., Shah M., Stanton V.P., Strobel S.A., Draths K.M., Wales J.L., Dervan P., Housman D.E., Altherr M., Shiang R., Thompson L., Fielder T., Wasmuth J.J., Tagle D., Valdes J., Elmer L., Allard M., Castilla L., Swaroop M., Blanchard K., Collins F.S., Snell R., Holloway T., Gillespie K., Datson N., Shaw D., Harper P.S. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntingtons-disease chromosomes. Cell 1993, 72:971-983.
62. Malik B., Nirmalananthan N., Bilsland L.G., La Spada A.R., Hanna M.G., Schiavo G., Gallo J.M., Greensmith L. Absence of disturbed axonal transport in spinal and bulbar muscular atrophy. Hum. Mol. Genet. 2011, 20:1776-1786.
63. Matias P.M., Donner P., Coelho R., Thomaz M., Peixoto C., Macedo S., Otto N., Joschko S., Scholz P., Wegg A., Basler S., Schafer M., Egner U., Carrondo M.A. Structural evidence for ligand specificity in the binding domain of the human androgen receptor. Implications for pathogenic gene mutations. J. Biol. Chem. 2000, 275:26164-26171.
64. 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. CREB-binding protein sequestration by expanded polyglutamine. Hum. Mol. Genet. 2000, 9:2197-2202.
65. Mhatre A.N., Trifiro M.A., Kaufman M., Kazemi-Esfarjani P., Figlewicz D., Rouleau G., Pinsky L. Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy. Nat. Genet. 1993, 5:184-188.
66. Minamiyama M., Katsuno M., Adachi H., Waza M., Sang C., Kobayashi Y., Tanaka F., Doyu M., Inukai A., Sobue G. Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Hum. Mol. Genet. 2004, 13:1183-1192.
67. Monks D.A., Johansen J.A., Mo K., Rao P., Eagleson B., Yu Z., Lieberman A.P., Breedlove S.M., Jordan C.L. Overexpression of wild-type androgen receptor in muscle recapitulates polyglutamine disease. Proc. Natl Acad. Sci. USA 2007, 104:18259-18264.
68. Montie H.L., Cho M.S., Holder L., Liu Y., Tsvetkov A.S., Finkbeiner S., Merry D.E. Cytoplasmic retention of polyglutamine-expanded androgen receptor ameliorates disease via autophagy in a mouse model of spinal and bulbar muscular atrophy. Hum. Mol. Genet. 2009, 18:1937-1950.
69. Morfini G., Pigino G., Szebenyi G., You Y., Pollema S., Brady S.T. JNK mediates pathogenic effects of polyglutamine-expanded androgen receptor on fast axonal transport. Nat. Neurosci. 2006, 9:907-916.
70. Nagafuchi S., Yanagisawa H., Sato K., Shirayama T., Ohsaki E., Bundo M., Takeda T., Tadokoro K., Kondo I., Murayama N., Tanaka Y., Kikushima H., Umino K., Kurosawa H., Furukawa T., Nihei K., Inoue T., Sano A., Komure O., Takahashi M., Yoshizawa T., Kanazawa I., Yamada M. Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p. Nat. Genet. 1994, 6:14-18.
71. Nakamura K., Jeong S.Y., Uchihara T., Anno M., Nagashima K., Nagashima T., Ikeda S., Tsuji S., Kanazawa I. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum. Mol. Genet. 2001, 10:1441-1448.
72. Nedelsky N.B., Pennuto M., Smith R.B., Palazzolo I., Moore J., Nie Z., Neale G., Taylor J.P. Native functions of the androgen receptor are essential to pathogenesis in a Drosophila model of spinobulbar muscular atrophy. Neuron 2010, 67:936-952.
73. Olsen D.B., Orngreen M.C., Vissing J. Aerobic training improves exercise performance in facioscapulohumeral muscular dystrophy. Neurology 2005, 64:1064-1066.
74. Orngreen M.C., Olsen D.B., Vissing J. Aerobic training in patients with myotonic dystrophy type 1. Ann. Neurol. 2005, 57:754-757.
75. Orr C.R., Montie H.L., Liu Y., Bolzoni E., Jenkins S.C., Wilson E.M., Joseph J.D., McDonnell D.P., Merry D.E. An interdomain interaction of the androgen receptor is required for its aggregation and toxicity in spinal and bulbar muscular atrophy. J. Biol. Chem. 2010, 285:35567-35577.
76. Orr H.T., Chung M.Y., Banfi S., Kwiatkowski T.J., Servadio A., Beaudet A.L., McCall A.E., Duvick L.A., Ranum L.P., Zoghbi H.Y. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat. Genet. 1993, 4:221-226.
77. Orr H.T., Zoghbi H.Y. Trinucleotide repeat disorders. Annu. Rev. Neurosci. 2007, 30:575-621.
78. Palazzolo I., Burnett B.G., Young J.E., Brenne P.L., La Spada A.R., Fischbeck K.H., Howell B.W., Pennuto M. Akt blocks ligand binding and protects against expanded polyglutamine androgen receptor toxicity. Hum. Mol. Genet. 2007, 16:1593-1603.
79. Palazzolo I., Nedelsky N.B., Askew C.E., Harmison G.G., Kasantsev A.G., Taylor J.P., Fischbeck K.H., Pennuto M. B2 attenuates polyglutamine-expanded androgen receptor toxicity in cell and fly models of spinal and bulbar muscular atrophy. J. Neurosci. Res. 2010, 88:2207-2216.
80. Palazzolo I., Stack C., Kong L., Musaro A., Adachi H., Katsuno M., Sobue G., Taylor J.P., Sumner C.J., Fischbeck K.H., Pennuto M. Overexpression of IGF-1 in muscle attenuates disease in a mouse model of spinal and bulbar muscular atrophy. Neuron 2009, 63:316-328.
81. 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. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 2007, 447:859-863.
82. Parboosingh J.S., Figlewicz D.A., Krizus A., Meininger V., Azad N.A., Newman D.S., Rouleau G.A. Spinobulbar muscular atrophy can mimic ALS: the importance of genetic testing in male patients with atypical ALS. Neurology 1997, 49:568-572.
83. Pennuto M., Palazzolo I., Poletti A. Post-translational modifications of expanded polyglutamine proteins: impact on neurotoxicity. Hum. Mol. Genet. 2009, 18:R40-47.
84. Pennuto M., Sambataro F. Pathogenesis of Polyglutamine Diseases. Encyclopedia of Life Science 2010, John Wiley & Sons, Ltd., Chichester, 1-9.
85. Perutz M.F., Johnson T., Suzuki M., Finch J.T. Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. Proc. Natl. Acad. Sci. USA 1994, 91:5355-5358.
86. Preisler N., Andersen G., Thogersen F., Crone C., Jeppesen T.D., Wibrand F., Vissing J. Effect of aerobic training in patients with spinal and bulbar muscular atrophy (Kennedy disease). Neurology 2009, 72:317-323.
87. Ranganathan S., Harmison G.G., Meyertholen K., Pennuto M., Burnett B.G., Fischbeck K.H. Mitochondrial abnormalities in spinal and bulbar muscular atrophy. Hum. Mol. Genet. 2009, 18:27-42.
88. Rechsteiner M., Rogers S.W. PEST sequences and regulation by proteolysis. Trends Biochem. Sci. 1996, 21:267-271.
89. Rusmini P., Simonini F., Crippa V., Bolzoni E., Onesto E., Cagnin M., Sau D., Ferri N., Poletti A. 17-AAG increases autophagic removal of mutant androgen receptor in spinal and bulbar muscular atrophy. Neurobiol. Dis. 2011, 41:83-95.
90. Saudou F., Finkbeiner S., Devys D., Greenberg M.E. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 1998, 95:55-66.
91. Schaufele F., Carbonell X., Guerbadot M., Borngraeber S., Chapman M.S., Ma A.A., Miner J.N., Diamond M.I. The structural basis of androgen receptor activation: intramolecular and intermolecular amino-carboxy interactions. Proc. Natl Acad. Sci. USA 2005, 102:9802-9807.
92. Schmidt B.J., Greenberg C.R., Allingham-Hawkins D.J., Spriggs E.L. Expression of X-linked bulbospinal muscular atrophy (Kennedy disease) in two homozygous women. Neurology 2002, 59:770-772.
93. Schneider C., Sepp-Lorenzino L., Nimmesgern E., Ouerfelli O., Danishefsky S., Rosen N., Hartl F.U. Pharmacologic shifting of a balance between protein refolding and degradation mediated by Hsp90. Proc. Natl Acad. Sci. USA 1996, 93:14536-14541.
94. Shao J., Diamond M.I. Polyglutamine diseases: emerging concepts in pathogenesis and therapy. Hum. Mol. Genet. 16 Spec No. 2007, 2:R115-R123.
95. Shi Q., Shih C.C., Lee K.H. Novel anti-prostate cancer curcumin analogues that enhance androgen receptor degradation activity. Anticancer Agents Med. Chem. 2009, 9:904-912.
96. Simental J.A., Sar M., Lane M.V., French F.S., Wilson E.M. Transcriptional activation and nuclear targeting signals of the human androgen receptor. J. Biol. Chem. 1991, 266:510-518.
97. Sopher B.L., Thomas P.S., 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. Androgen receptor YAC transgenic mice recapitulate SBMA motor neuronopathy and implicate VEGF164 in the motor neuron degeneration. Neuron 2004, 41:687-699.
98. Stanford J.L., Just J.J., Gibbs M., Wicklund K.G., Neal C.L., Blumenstein B.A., Ostrander E.A. Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk. Cancer Res. 1997, 57:1194-1198.
99. Su S., Jou S., Cheng W., Lin T., Li J., Huang C., Lee Y., Soong B., Liu C. Mitochondrial DNA damage in spinal and bulbar muscular atrophy patients and carriers. Clin. Chim. Acta 2010, 411:626-630.
100. Sveen M.L., Jeppesen T.D., Hauerslev S., Krag T.O., Vissing J. Endurance training: an effective and safe treatment for patients with LGMD2I. Neurology 2007, 68:59-61.
101. Takahashi T., Katada S., Onodera O. Polyglutamine diseases: where does toxicity come from? What is toxicity? Where are we going?. J. Mol. Cell Biol. 2010, 2:180-191.
102. Takeyama K., Ito S., Yamamoto A., Tanimoto H., Furutani T., Kanuka H., Miura M., Tabata T., Kato S. Androgen-dependent neurodegeneration by polyglutamine-expanded human androgen receptor in Drosophila. Neuron 2002, 35:855-864.
103. Tanner T., Claessens F., Haelens A. The hinge region of the androgen receptor plays a role in proteasome-mediated transcriptional activation. Ann. N. Y. Acad. Sci. 2004, 1030:587-592.
104. Tanner T.M., Denayer S., Geverts B., Van Tilborgh N., Kerkhofs S., Helsen C., Spans L., Dubois V., Houtsmuller A.B., Claessens F., Haelens A. A 629RKLKK633 motif in the hinge region controls the androgen receptor at multiple levels. Cell. Mol. Life Sci. 2010, 67:1919-1927.
105. Taylor J.P., Taye A.A., Campbell C., Kazemi-Esfarjani P., Fischbeck K.H., Min K.T. Aberrant histone acetylation, altered transcription, and retinal degeneration in a Drosophila model of polyglutamine disease are rescued by CREB-binding protein. Genes Dev. 2003, 17:1463-1468.
106. Thomas M., Dadgar N., Aphale A., Harrell J.M., Kunkel R., Pratt W.B., Lieberman A.P. Androgen receptor acetylation site mutations cause trafficking defects, misfolding, and aggregation similar to expanded glutamine tracts. J. Biol. Chem. 2004, 279:8389-8395.
107. Thomas P.S., Fraley G.S., Damian V., Woodke L.B., Zapata F., Sopher B.L., Plymate S.R., La Spada A.R. Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy. Hum. Mol. Genet. 2006, 15:2225-2238.
108. Tokui K., Adachi H., Waza M., Katsuno M., Minamiyama M., Doi H., Tanaka K., Hamazaki J., Murata S., Tanaka F., Sobue G. 17-DMAG ameliorates polyglutamine-mediated motor neuron degeneration through well-preserved proteasome function in an SBMA model mouse. Hum. Mol. Genet. 2009, 18:898-910.
109. Trapman J., Klaassen P., Kuiper G.G., van der Korput J.A., Faber P.W., van Rooij H.C., Geurts van Kessel A., Voorhorst M.M., Mulder E., Brinkmann A.O. Cloning, structure and expression of a cDNA encoding the human androgen receptor. Biochem. Biophys. Res. Commun. 1988, 153:241-248.
110. Tut T.G., Ghadessy F.J., Trifiro M.A., Pinsky L., Yong E.L. Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. J. Clin. Endocrinol. Metab. 1997, 82:3777-3782.
111. van Royen M.E., Cunha S.M., Brink M.C., Mattern K.A., Nigg A.L., Dubbink H.J., Verschure P.J., Trapman J., Houtsmuller A.B. Compartmentalization of androgen receptor protein-protein interactions in living cells. J. Cell Biol. 2007, 177:63-72.
112. Wang Q., Udayakumar T.S., Vasaitis T.S., Brodie A.M., Fondell J.D. Mechanistic relationship between androgen receptor polyglutamine tract truncation and androgen-dependent transcriptional hyperactivity in prostate cancer cells. J. Biol. Chem. 2004, 279:17319-17328.
113. Warnmark A., Treuter E., Wright A.P., Gustafsson J.A. Activation functions 1 and 2 of nuclear receptors: molecular strategies for transcriptional activation. Mol. Endocrinol. 2003, 17:1901-1909.
114. Waza M., Adachi H., Katsuno M., Minamiyama M., Sang C., Tanaka F., Inukai A., Doyu M., Sobue G. 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. Nat. Med. 2005, 11:1088-1095.
115. Werner R., Holterhus P.M., Binder G., Schwarz H.P., Morlot M., Struve D., Marschke C., Hiort O. The A645D mutation in the hinge region of the human androgen receptor (AR) gene modulates AR activity, depending on the context of the polymorphic glutamine and glycine repeats. J. Clin. Endocrinol. Metab. 2006, 91:3515-3520.
116. 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. ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor. Nat. Med. 2007, 13:348-353.
117. Young J.E., Garden G.A., Martinez R.A., Tanaka F., Sandoval C.M., Smith A.C., Sopher B.L., Lin A., Fischbeck K.H., Ellerby L.M., Morrison R.S., Taylor J.P., La Spada A.R. Polyglutamine-expanded androgen receptor truncation fragments activate a Bax-dependent apoptotic cascade mediated by DP5/Hrk. J. Neurosci. 2009, 29:1987-1997.
118. Yu Z., Dadgar N., Albertelli M., Gruis K., Jordan C., Robins D.M., Lieberman A.P. Androgen-dependent pathology demonstrates myopathic contribution to the Kennedy disease phenotype in a mouse knock-in model. J. Clin. Invest. 2006, 116:2663-2672.
119. Zhuchenko O., Bailey J., Bonnen P., Ashizawa T., Stockton D.W., Amos C., Dobyns W.B., Subramony S.H., Zoghbi H.Y., Lee C.C. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat. Genet. 1997, 15:62-69.