Androgen-dependent neurodegeneration by polyglutamine-expanded human androgen receptor in Drosophila

Ken Ichi Takeyama, Saya Ito, Ayako Yamamoto, Hiromu Tanimoto, Takashi Furutani, Hirotaka Kanuka, Masayuki Miura, Tetsuya Tabata, Shigeaki Kato

Research output: Contribution to journalArticlepeer-review

258 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)855-864
Number of pages10
JournalNeuron
Volume35
Issue number5
DOIs
Publication statusPublished - 2002 Aug 29
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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