LAUSR

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 The aim of this review is to help researchers both working on this research topic or not to have a comprehensive overview on 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 also with the help of figures, to conclude with a comprehensive overview on the most important GSK-3β and multitarget inhibitors. For all discussed compounds, the structure and IC50 values at the target kinase have been reported. CONCLUSION GSK-3β is involved in several signaling pathways both in neurons as well as in 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. In fact, some compounds are now under clinical trials. Despite this, pharmacodynamic and ADME/Tox profiles of the compounds were often not fully characterized and this is deleterious in such a complex system.