Recent Advances in the Discovery of GSK-3 Inhibitors from Synthetic Origin in the Treatment of Neurological Disorders
Background: Glycogen synthase kinase 3 (GSK-3) is a serine/threonine kinase enzyme which controlled the neuronal functions such as neurite outgrowth, synapse formation, neurotransmission, and neurogenesis. The enzyme has two subunits as GSK-3α and GSK-3β. 4ACC, 1Q3D, 3AFG, 1UV5, 1Q5K are the important GSK-3 receptors isolated from Homo sapiens and Mus musculus. This enzyme mainly phosphorylates Tau protein with increased amount in neuronal fibres altogether with beta-amyloid plaques cause neuronal defects like Alzheimer, Parkinson’s and many more. Objective: We investigated the developments of various synthetic GSK-3 inhibitors responsible for the prevention and treatment of neurological disorders like Alzheimer disease, bipolar disorders, antidepressant, neuroprotective etc. Results and Conclusion: It was observed that structures of the GSK-3 inhibitors comprised of benzopyridine, benzthiazole, pyrazole, pyrazine, dioxolo-benzoxazin, oxadiazole, benzimidazole in the skeletal with cyclopropylamide, phenyl carbamothioate, 3-[(propan-2-yl)oxy]propan-1-amine in side chain. The molecules were evaluated against the effectivity of GSK-3, human adenosine kinase, cyclin dependent kinase, and phosphodiesterase-4 along with tail suspension test, forced swim test, percent neuronal survival and other cognitive behaviour. The observations confirmed the remarkable effects of the synthesized molecules to conquer Alzheimer, Parkinson’s depression, psychosis and other forms of neurological disorders.