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一种与β淀粉样肽结合并在阿尔茨海默病中介导神经毒性的细胞内蛋白质。

An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease.

作者信息

Yan S D, Fu J, Soto C, Chen X, Zhu H, Al-Mohanna F, Collison K, Zhu A, Stern E, Saido T, Tohyama M, Ogawa S, Roher A, Stern D

机构信息

Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.

出版信息

Nature. 1997 Oct 16;389(6652):689-95. doi: 10.1038/39522.

Abstract

Amyloid-beta is a neurotoxic peptide which is implicated in the pathogenesis of Alzheimer's disease. It binds an intracellular polypeptide known as ERAB, thought to be a hydroxysteroid dehydrogenase enzyme, which is expressed in normal tissues, but is overexpressed in neurons affected in Alzheimer's disease. ERAB immunoprecipitates with amyloid-beta, and when cell cultures are exposed to amyloid-beta, ERAB inside the cell is rapidly redistributed to the plasma membrane. The toxic effect of amyloid-beta on these cells is prevented by blocking ERAB and is enhanced by overexpression of ERAB. By interacting with intracellular amyloid-beta, ERAB may therefore contribute to the neuronal dysfunction associated with Alzheimer's disease.

摘要

β-淀粉样蛋白是一种神经毒性肽,与阿尔茨海默病的发病机制有关。它与一种称为ERAB的细胞内多肽结合,ERAB被认为是一种羟基类固醇脱氢酶,在正常组织中表达,但在阿尔茨海默病受累的神经元中过度表达。ERAB与β-淀粉样蛋白免疫共沉淀,当细胞培养物暴露于β-淀粉样蛋白时,细胞内的ERAB会迅速重新分布到质膜。通过阻断ERAB可预防β-淀粉样蛋白对这些细胞的毒性作用,而ERAB的过表达则会增强这种毒性作用。因此,通过与细胞内的β-淀粉样蛋白相互作用,ERAB可能导致与阿尔茨海默病相关的神经元功能障碍。

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