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Hsp90 is involved in the folding, activation, and assembly of its client proteins in association with its co\u2010chaperones. Because numerous oncoproteins belonging to the Hsp90 client protein family are selectively degraded by Hsp90 inhibitors, 17\u2010allylamino\u201017\u2010demethoxygeldanamycin (17\u2010AAG), a first\u2010in\u2010class Hsp90 inhibitor, is now under clinical trials as a novel molecular\u2010targeted agent for a wide range of malignancies. In spinal and bulbar muscular atrophy (SBMA), the pathogenic gene product is polyglutamine (polyQ)\u2010expanded androgen receptor (AR), which belongs to the Hsp90 client protein family and is known to be degraded by 17\u2010AAG. We have recently demonstrated that administration of an anticancer agent 17\u2010AAG significantly ameliorated polyQ\u2010mediated motor neuron degeneration by reducing the total amount of mutant AR. The ability of 17\u2010AAG to degrade mutant protein would be directly applicable to SBMA and other neurodegenerative diseases in which the disease\u2010causing proteins also belong to the Hsp90 client protein family. Our proposed therapeutic approach using a novel anticancer agent 17\u2010AAG has emerged as a candidate for molecular\u2010targeted therapies for neurodegenerative diseases.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1377.012","type":"journal-article","created":{"date-parts":[[2006,12,21]],"date-time":"2006-12-21T19:28:17Z","timestamp":1166729297000},"page":"21-34","source":"Crossref","is-referenced-by-count":41,"title":["Alleviating Neurodegeneration by an Anticancer Agent"],"prefix":"10.1111","volume":"1086","author":[{"given":"MASAHIRO","family":"WAZA","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HIROAKI","family":"ADACHI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MASAHISA","family":"KATSUNO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MAKOTO","family":"MINAMIYAMA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FUMIAKI","family":"TANAKA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GEN","family":"SOBUE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,12,5]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1066"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1690"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/352077a0"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/112.1.209"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.9.1253"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410320517"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl096"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh381"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.45.28697"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0259150"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2004.03.001"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/153537020322800201"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4914(02)02316-X"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1379\/1466-1268(2002)007<0055:EOGOAR>2.0.CO;2"},{"key":"e_1_2_9_16_2","first-page":"986","article-title":"17\u2010Allylamino\u201017\u2010demethoxygeldanamycin induces the degradation of androgen receptor and HER\u20102\/neu and inhibits the growth of prostate cancer xenografts","volume":"8","author":"Solit D.B.","year":"2002","journal-title":"Clin. 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