GSK-3
GSK-3, a key component in glycogen metabolism, has been heavily implicated in the incidence and progression of a number of diseases including diabetes, cancer and AD. Its most well-known function is constitutive phosphorylation of glycogen synthase. Conversely, GSK-3 inhibition prevents Tau hyperphosphorylation and serves as a protectant against neuronal apoptosis, as well as blocking the accumulation and toxicity of Ab/tau. Unlike most other kinases, GSK-3 is constitutively active, and its effects are regulated primarily through inhibition of its activity. Increased expression and activity of GSK-3 have been implicated both in Type II diabetes and AD, whereas, decreases in its constitutive cellular function are closely linked to various forms of cancer. The therapeutic potential of GSK-3 inhibitors has become a major area of pharmaceutical interest, and the development of GSK-3 targeted therapeutics hold excellent opportunities for the treatment of GSK-3-associated disease states.Inhibition of GSK-3b
Inhibition of GSK-3b by Ro31-8220. GSK-3b, active (Millipore cat. no. 14-306) was incubated with various concentrations of Ro31-8220 and assayed by measuring incorporation of radioactivity from g3 3p-ATP into PhosphoGlycogen Synthase Peptide-2 (Millipore cat.no. 12-241). IC50s were determined at both 10 and 100 mM ATP and were 16 nM and 79 nM respectively. |
