糖原合成酶激酶-3(GSK-3)是一种广泛表达的丝氨酸/苏氨酸激酶,可调节多种细胞过程,包括增殖,分化与死亡哺乳动物具有两种结构上相似的同种型GSK-3α和β,它们具有重叠和独特的功能。在这两个人中,对GSK-3β进行了更详细的研究(和审查),通常是事后对GSK-3α的分析。现在很明显,系统性的,GSK-3β或GSK-3α/β的慢性抑制在临床上是不可行的,并且如果实现,则可能导致不利的临床状况。新的证据表明GSK-3α在脂肪酸积累中的重要和特定作用,胰岛素抵抗,淀粉样β蛋白前体代谢,动脉粥样硬化,心肌病,纤维化,老化,生育力,以及各种癌症。GSK-3α的选择性靶向可以提供新的治疗机会来缓解许多病理状况。在这次审查中,我们评估了GSK-3α在多种病理生理环境中作用的证据。
Glycogen synthase kinase-3 (GSK-3) is a widely expressed serine/threonine kinase regulates a variety of cellular processes including proliferation, differentiation and death. Mammals harbor two structurally similar isoforms GSK-3α and β that have overlapping as well as unique functions. Of the two, GSK-3β has been studied (and reviewed) in far greater detail with analysis of GSK-3α often as an afterthought. It is now evident that systemic, chronic inhibition of either GSK-3β or both GSK-3α/β is not clinically feasible and if achieved would likely lead to adverse clinical conditions. Emerging evidence suggests important and specific roles for GSK-3α in fatty acid accumulation, insulin resistance, amyloid-β-protein precursor metabolism, atherosclerosis, cardiomyopathy, fibrosis, aging, fertility, and in a variety of cancers. Selective targeting of GSK-3α may present a novel therapeutic opportunity to alleviate a number of pathological conditions. In this review, we assess the evidence for roles of GSK-3α in a variety of pathophysiological settings.