GSK3 in Alzheimer's disease: mind the isoforms.
GSK3 in Alzheimer's disease: mind the isoforms.
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DOI：
10.3233/jad-131661
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发表时间：
2014
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影响因子：
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通讯作者：
Ma T
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文献类型：
--
作者：
Ma T
了解阿尔茨海默病（AD）中出错的分子信号通路将为开发这种毁灭性神经退行性疾病的新疗法提供见解。先前的工作已经确定，过度活跃的糖原合成酶激酶-3（GSK 3）与“散发性”和“遗传性”形式的AD相关联，表明GSK 3在AD发病机制中起关键作用。因此，抑制GSK 3活性作为AD的潜在治疗干预已被深入研究。GSK 3有两种亚型：GSK 3 α和GSK 3 β。值得注意的是，最近的研究表明GSK 3的α和β亚型中的每一种对AD发病机制的特定贡献，表明两种亚型在疾病中的作用。在这里，我回顾了最近的相关工作，调查异构体特异性作用的GSK 3在AD的病理生理学，突出的新兴作用的GSK 3 α，这在很大程度上被忽视，有利于更广泛的研究GSK 3 β。
Understanding the molecular signaling pathways that go awry in Alzheimer’s disease (AD) would provide insights into developing novel therapies for this devastating neurodegenerative disease. Previous work has established that hyperactive glycogen synthase kinase-3 (GSK3) is linked to both “sporadic” and “genetic” forms of AD, suggesting a crucial role of GSK3 in AD pathogenesis. Therefore, inhibition of GSK3 activity has been intensely investigated as a potential therapeutic intervention for AD. GSK3 exists in two isoforms: GSK3α and GSK3β. Markedly, recent studies indicate specific contributions of each of the α and β isoforms of GSK3 to AD pathogenesis, suggesting a role of both isoforms in the disease. Here I review recent relevant work investigating isoform-specific roles of GSK3 in AD pathophysiology, highlighting the emerging role of GSK3α, which has been largely overlooked in favor of the more extensive studies of GSK3β.