GSK3 has gained a considerable attention of researchers in the late 1970s as an inevitable drug target
to treat diabetes. Furthermore, it was found to have a key role in the development of diseases like cancer and
neurodegeneration (ND). A broad spectrum of GSK3 inhibitors have been discovered from time to time in order
to curb these diseases. Inhibition of GSK3 by insulin boosts the dephosphorylation of glycogen synthase, hence
its activation to convert UDP glucose into glycogen. Lack of insulin and insulin-resistance is supposed to be the
cause of type 2 diabetes (Diabetes mellitus). Additionally, GSK3 stabilizes the components of beta-catenin complex,
hence promotes oncogenesis. Phosphorylation of GSK3 by Akt and some other kinases also favours the
carcinogenesis. However, in some cases GSK3 has tumor supressing character. GSK3 has been found to have a
prominent role in the formation of amyloid plaques and neurofibrillary tangles (abnormal protein accumulations)
which are the main suspects of Alzheimer's disease (AD). GSK3 inhibitors have been reported to have amyloidbeta
disaggregation property and have been found to promote the adult hippocampal neurogenesis in vivo as well
as in vitro. This manuscript thoroughly reviews the involvement of GSK3 in diabetes, cancer and ND. Furthermore,
development of GSK3 inhibitors as antidiabetes, anticancer and antineurodegenerative agents focusing
mainly on lead optimization has been discussed.
Keywords: GSK3, diabetes, cancer, neurodegeneration, inhibitor, insulin.
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