Glycogen Synthase Kinase 3β Involvement in Neuroinflammation and Neurodegenerative Diseases

Background: GSK-3β activity has been strictly related to neuroinflammation and neurodegeneration. Alzheimer’s disease is the most studied neurodegenerative disease, but GSK-3β seems to be involved in almost all neurodegenerative diseases, including Parkinson’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington’s disease, and the autoimmune disease multiple sclerosis. Objective: This review aims to help researchers both working on this research topic or not to have a comprehensive overview of GSK-3β in the context of neuroinflammation and neurodegeneration. Method: Literature has been searched using PubMed and SciFinder databases by inserting specific keywords. A total of more than 500 articles have been discussed. Results: First of all, the structure and regulation of the kinase were briefly discussed, and then, specific GSK-3β implications in neuroinflammation and neurodegenerative diseases were illustrated with the help of figures, to conclude with a comprehensive overview on the most important GSK-3β and multitarget inhibitors. The structure and IC50 values at the target kinase have been reported for all the discussed compounds. Conclusion: GSK-3β is involved in several signaling pathways in neurons, glial cells and immune cells. The fine regulation and interconnection of all these pathways are at the base of the rationale use of GSK-3β inhibitors in neuroinflammation and neurodegeneration. Some compounds are now under clinical trials. Despite this, the compounds’ pharmacodynamic and ADME/Tox profiles were often not fully characterized which is deleterious in such a complex system.