| RRC ID |
286
|
| 著者 |
Takeyama K, Ito S, Yamamoto A, Tanimoto H, Furutani T, Kanuka H, Miura M, Tabata T, Kato S.
|
| タイトル |
Androgen-dependent neurodegeneration by polyglutamine-expanded human androgen receptor in Drosophila.
|
| ジャーナル |
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.
|
| 巻・号 |
35(5)
|
| ページ |
855-64
|
| 公開日 |
2002-8-29
|
| DOI |
10.1016/s0896-6273(02)00875-9
|
| 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 |
14.415
|
| 引用数 |
224
|
|
WOS 分野
|
NEUROSCIENCES
|
| リソース情報 |
| ショウジョウバエ |
|
