Emerging roles of GSK-3α in pathophysiology: Emphasis on cardio-metabolic disorders

Publication date: Available online 27 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Firdos Ahmad, James R. WoodgettAbstractGlycogen 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.
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research