![]() Here we review the state of the art of GSK-3 inhibitors with focus on their biological activities in neurons and neurological disorders. A major challenge in the field is achieving specificity, and advanced structure-based computational studies are conducted to improve GSK-3 inhibitor specificity and possibly to ensure targeting of specific GSK-3 isozymes. ![]() Regarding the mechanism of inhibition, we can find ATP-competitive inhibitors, non-ATP-competitive inhibitors, and substrate–competitive inhibitors. These include inhibitors isolated from natural sources, cations, and synthetic small molecules. The reported GSK-3 inhibitors are of diverse chemotypes and mechanisms of action. ![]() This supported the hypothesis that inhibition of GSK-3 will have therapeutic benefit and intensive efforts have been made in the search for and design of selective GSK-3 inhibitors. Aberrant GSK-3 activity has been linked with several human diseases including diabetes, inflammation, and neurodegenerative and psychiatric disorders (Eldar-Finkelman, 2002 Doble and Woodgett, 2003 Gould et al., 2004b Jope et al., 2007 Hernandez and Avila, 2008 Hooper et al., 2008 Hur and Zhou, 2010). The serine/threonine kinase GSK-3 is a conserved signaling molecule with essential roles in diverse biological processes.
0 Comments
Leave a Reply. |