Glycogen Synthase Kinase-3β: A Key Player in Alzheimer's Disease Pathogenesis and Therapeutic Targeting

About 70% of dementia cases are caused by Alzheimer's disease (AD), making it the most common cause. Nearly 7 million people in the US currently have AD, and by 2050, that number is expected to nearly double, creating serious socioeconomic problems. A cure for AD is still elusive despite a great deal of research. Numerous signaling pathways linked to AD neuropathology have been the subject of recent studies, with glycogen synthase kinase-3β (GSK3-β) emerging as a potential therapeutic target. GSK3-β is a constitutively active serine/threonine kinase that is essential for many biological functions, such as gene transcription and glycogen metabolism. It has a complex role in the pathophysiology of AD, impacting important indicators like tau phosphorylation, amyloid-β production, neuroinflammation, memory loss, and synaptic dysfunction. The goal of this review article is to give a thorough overview of GSK3-β neurobiology with a focus on how it affects signaling pathways linked to the pathophysiology of AD. It also evaluates the feasibility of targeting GSK3-β as a therapeutic approach for AD by examining the state of GSK3-β inhibitor development in preclinical and clinical trials. Preclinical research has shown encouraging results, but there are still obstacles in converting these discoveries into successful clinical therapies, including problems with drug specificity, safety, and brain penetration. However, there is still hope for creating new therapeutic strategies to fight this debilitating neurodegenerative disease, thanks to continued research into GSK3-β inhibitors.