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凋亡诱导因子及其衔接蛋白——寻找新的参与者。

AICD and its adaptors - in search of new players.

作者信息

Raychaudhuri Mithu, Mukhopadhyay Debashis

机构信息

Structural Genomics Section, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700 064, India.

出版信息

J Alzheimers Dis. 2007 Jun;11(3):343-58. doi: 10.3233/jad-2007-11311.

Abstract

In view of the emerging evidence that amyloid-beta load in the brain and neuronal deficits are possibly independent events and the increasing importance of downstream molecular cascades in Alzheimer's Disease (AD) pathogenesis, the role of Amyloid Intracellular C-terminal Domain (AICD) is evaluated. This C-terminal fragment of Amyloid-beta protein precursor (AbetaPP) is cytotoxic and is a major component of AD brain. Different portions of AICD bind to different 'adaptors' and are seen to take part in various cellular events including AbetaPP processing and trafficking, apoptosis, neuronal growth and regulation of gene transcription. Phosphorylation also plays an important role in terms of choice of binding partners. The review emphasizes the dynamics of the network created by AICD interactions and points to possible alternative routes of AD like neurodegeneration.

摘要

鉴于新出现的证据表明大脑中的β淀粉样蛋白负荷和神经元缺陷可能是独立事件,以及下游分子级联反应在阿尔茨海默病(AD)发病机制中的重要性日益增加,对淀粉样蛋白细胞内C末端结构域(AICD)的作用进行了评估。淀粉样β蛋白前体(AbetaPP)的这个C末端片段具有细胞毒性,是AD大脑的主要成分。AICD的不同部分与不同的“衔接蛋白”结合,并参与各种细胞活动,包括AbetaPP的加工和运输、细胞凋亡、神经元生长和基因转录调控。磷酸化在结合伙伴的选择方面也起着重要作用。该综述强调了由AICD相互作用形成的网络的动态性,并指出了类似AD的神经退行性变的可能替代途径。

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