2003年3月
Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila
NEURON
- ,
- ,
- ,
- ,
- 巻
- 37
- 号
- 6
- 開始ページ
- 911
- 終了ページ
- 924
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/S0896-6273(03)00143-0
- 出版者・発行元
- CELL PRESS
Parkin, an E3 ubiquitin ligase that degrades proteins with aberrant conformations, is associated with autosomal recessive juvenile Parkinsonism (AR-JP). The molecular basis of selective neuronal death in AR-JP is unknown. Here we show in an organismal system that panneuronal expression of Parkin substrate Pael-R causes age-dependent selective degeneration of Drosophila dopaminergic (DA) neurons. Coexpression of Parkin degrades Pael-R and suppresses its toxicity, whereas interfering with endogenous Drosophila Parkin function promotes Pael-R accumulation and augments its toxicity. Furthermore, overexpression of Parkin can mitigate a.-Synuclein-induced neuritic pathology and suppress its toxicity. Our study implicates Parkin as a central player in the molecular pathway of Parkinson's disease (PD) and suggests that manipulating Parkin expression may provide a novel avenue of PD therapy.
- リンク情報
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- DOI
- https://doi.org/10.1016/S0896-6273(03)00143-0
- CiNii Articles
- http://ci.nii.ac.jp/naid/30010677109
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/12670421
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000181899600006&DestApp=WOS_CPL
- ID情報
-
- DOI : 10.1016/S0896-6273(03)00143-0
- ISSN : 0896-6273
- CiNii Articles ID : 30010677109
- PubMed ID : 12670421
- Web of Science ID : WOS:000181899600006