α-Synuclein and the Parkinson's disease-related mutant Ala53Thr-α-synuclein do not undergo proteasomal degradation in HEK293 and neuronal cells

被引:97
作者
Ancolio, K
da Costa, CA
Uéda, K
Checler, F
机构
[1] CNRS, Inst Pharmacol Mol & Cellulaire, UPR411, F-06560 Valbonne, France
[2] Tokyo Inst Psychiat, Dept Neurochem, Tokyo 1568585, Japan
关键词
alpha-synuclein; Ala53Thr-alpha-synuclein; proteasome; degradation; Parkinson disease; Alzheimer's disease; neurons; HEK293; cells;
D O I
10.1016/S0304-3940(00)01049-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Synucleins are neuronal proteins detectable in the neuropathological lesions of several cerebral disorders. Thus, alpha-synuclein immunoreactivity is found in Lewy bodies, the histopathological hallmark of sporadic Parkinson disease-affected brains. When mutated, alpha-synuclein seems to be responsible for some familial forms of Parkinson disease. As Lewy bodies are enriched in ubiquitinated structures and also contain proteasome-related immunoreactivity, it could be hypothesized that the proteasome contributes to the cellular degradation of alpha-synucleins, thereby controlling their concentration-dependent aggregation process. Here, we first demonstrate that alpha-synuclein is not ubiquitinated in HEK293 cells. Furthermore, by means of two specific inhibitors, we show that wild type and Ala53Thr alpha-synuclein do not behave as proteasome substrates in HEK293 cells a nd mu ri ne neurons. Our study indicates that the proteasome does not contribute to the control of cellular synucleins concentration and therefore, unlikely participates to cerebral alpha-synucleinopathies. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:79 / 82
页数:4
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