RRC ID 286
Author Takeyama K, Ito S, Yamamoto A, Tanimoto H, Furutani T, Kanuka H, Miura M, Tabata T, Kato S.
Title Androgen-dependent neurodegeneration by polyglutamine-expanded human androgen receptor in Drosophila.
Journal Neuron
Abstract Spinal and bulbar muscular atrophy (SBMA) is an X-linked, adult-onset, neurodegenerative disorder affecting only males and is caused by expanded polyglutamine (polyQ) stretches in the N-terminal A/B domain of human androgen receptor (hAR). Although no overt phenotype was detected in adult fly eye photoreceptor neurons expressing mutant hAR (polyQ 52), ingestion of androgen or its known antagonists caused marked neurodegeneration with nuclear localization and structural alteration of the hAR mutant. Ligand-independent toxicity was detected with a truncated polyQ-expanded A/B domain alone, which was attenuated with cytosolic trapping by coexpression of the unliganded hAR E/F ligand binding domain. Thus, our findings suggest that the full binding of androgen to the polyQ-expanded hAR mutants leads to structural alteration with nuclear translocation that eventually results in the onset of SBMA in male patients.
Volume 35(5)
Pages 855-64
Published 2002-8-29
PII S0896627302008759
PMID 12372281
MeSH Animals Animals, Genetically Modified / genetics Binding Sites / genetics COS Cells Drosophila / genetics* Gene Targeting Humans Muscular Atrophy, Spinal / genetics Muscular Atrophy, Spinal / metabolism Neurodegenerative Diseases / genetics Neurodegenerative Diseases / metabolism* Peptides / metabolism* Photoreceptor Cells, Invertebrate / metabolism Receptors, Androgen / genetics Receptors, Androgen / metabolism Receptors, Androgen / physiology*
IF 14.319
Times Cited 204