title: Pathogenic mechanisms and therapeutic strategies in spinobulbar muscular atrophy.
abstract: We review the genetic and clinical features of spinobulbar muscular atrophy (SBMA), a progressive neuromuscular disorder caused by a CAG/glutamine tract expansion in the androgen receptor. SBMA was the first polyglutamine disease to be discovered, and we compare and contrast it with related degenerative disorders of the nervous system caused by expanded glutamine tracts. We review the cellular and animals models that have been most widely used to study this disorder, and highlight insights into disease pathogenesis derived from this work. These model systems have revealed critical aspects of the disease, including its hormone dependence, a feature that underlies disease occurrence only in men with the mutant allele. We discuss how this and other findings have been translated to clinical trials for SBMA patients, and examine emerging therapeutic targets that have been identified by recent work.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Chua
authors.affiliation: Department of Pathology, University of Michigan Medical School, 3510 MSRB1, 1150 W. Medical Center Dr., Ann Arbor, Michigan 48109-0605, USA. liebermn@umich.edu.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lieberman
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D020966:Muscular Disorders, Atrophic / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018832:Molecular Chaperones
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