Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson's disease
Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson's disease
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DOI：
10.1126/science.1067389
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发表时间：
2002-02-01
期刊：
影响因子：
56.9
通讯作者：
Bonini, NM
中科院分区：
文献类型：
--
作者：
Auluck, PK;Chan, HYE;Bonini, NM
帕金森病是一种运动障碍，其特征是黑质致密部多巴胺能神经元变性。在黑腹果蝇中，当定向表达α - 突触核蛋白时也会发生多巴胺能神经元丢失，α - 突触核蛋白是一种与帕金森病发病机制有关的蛋白质，也是蛋白质性路易小体的主要成分。我们报道，分子伴侣Hsp70的定向表达可防止果蝇中与α - 突触核蛋白相关的多巴胺能神经元丢失，并且干扰内源性伴侣活性会加速α - 突触核蛋白的毒性。此外，对人死后组织中的路易小体进行分子伴侣免疫染色，也表明伴侣可能在帕金森病的进展中起作用。
Parkinson's disease is a movement disorder characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Dopaminergic neuronal loss also occurs in Drosophila melanogaster upon directed expression of alpha-synuclein, a protein implicated in the pathogenesis of Parkinson's disease and a major component of proteinaceous Lewy bodies. We report that directed expression of the molecular chaperone, Hsp70 prevented dopaminergic neuronal loss associated with alpha-synuclein in Drosophila and that interference with endogenous chaperone activity accelerated alpha-synuclein toxicity. Furthermore, Lewy bodies in human postmortem tissue immunostained for molecular chaperones, also suggesting that chaperones may play a role in Parkinson's disease progression.