Regulation of cell survival mechanisms in Alzheimer's disease by glycogen synthase kinase-3.
Regulation of cell survival mechanisms in Alzheimer's disease by glycogen synthase kinase-3.
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DOI：
10.4061/2011/861072
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发表时间：
2011
影响因子：
--
通讯作者：
Jope RS
中科院分区：
文献类型：
--
作者：
Mines MA;Beurel E;Jope RS
糖原合成酶激酶-3（GSK 3）作为阿尔茨海默病病理学的重要贡献者，已经出现了关键作用。GSK 3参与阿尔茨海默病病理学和神经元损失的证据来自GSK 3过表达的研究、GSK 3定位研究、GSK 3与淀粉样β肽（Aβ）之间的多种关系、GSK 3与微管相关tau蛋白之间的相互作用以及GSK 3介导的凋亡性细胞死亡。凋亡信号通过内源性途径或外源性途径进行。GSK 3被很好地确立为促进由许多损伤诱导的内在凋亡信号传导，其中一些损伤可能导致阿尔茨海默病中的神经元损失。尤其重要的是，有证据表明GSK 3促进Aβ诱导的内在凋亡信号传导。GSK 3似乎通过调节细胞凋亡信号通路中的蛋白质和通过调节调节参与细胞凋亡的蛋白质表达的转录因子来促进内在细胞凋亡信号传导。因此，GSK 3似乎有助于阿尔茨海默病中的几种神经病理学机制，包括阿尔茨海默病介导的神经元损失。
A pivotal role has emerged for glycogen synthase kinase-3 (GSK3) as an important contributor to Alzheimer's disease pathology. Evidence for the involvement of GSK3 in Alzheimer's disease pathology and neuronal loss comes from studies of GSK3 overexpression, GSK3 localization studies, multiple relationships between GSK3 and amyloid β-peptide (Aβ), interactions between GSK3 and the microtubule-associated tau protein, and GSK3-mediated apoptotic cell death. Apoptotic signaling proceeds by either an intrinsic pathway or an extrinsic pathway. GSK3 is well established to promote intrinsic apoptotic signaling induced by many insults, several of which may contribute to neuronal loss in Alzheimer's disease. Particularly important is evidence that GSK3 promotes intrinsic apoptotic signaling induced by Aβ. GSK3 appears to promote intrinsic apoptotic signaling by modulating proteins in the apoptosis signaling pathway and by modulating transcription factors that regulate the expression of proteins involved in apoptosis. Thus, GSK3 appears to contribute to several neuropathological mechanisms in Alzheimer's disease, including apoptosis-mediated neuronal loss.