Alzheimer's disease (AD) is the most common form of neurodegenerative disorder with dementia, accounting for approximately 70% of the all cases. Currently, 5.8 million people in the U.S. are living with AD and by 2050 this number is expected to double resulting in a significant socio-economic burden. Despite intensive research, the exact mechanisms that trigger AD are still not known and at the present there is no cure for it. In recent years, many signaling pathways associated with AD neuropathology have been explored as possible candidate targets for the treatment of this condition including glycogen synthase kinase-3β (GSK3-β). GSK3-β is considered a key player in AD pathophysiology since dysregulation of this kinase influences all the major hallmarks of the disease including: tau phosphorylation, amyloid-β production, memory, neurogenesis and synaptic function. The present review summarizes the current understanding of the GSK3-β neurobiology with particular emphasis on its effects on specific signaling pathways associated with AD pathophysiology. Moreover, it discusses the feasibility of targeting GSK3-β for AD treatment and provides a summary of the current research effort to develop GSK3-β inhibitors in preclinical and clinical studies.
Keywords: Alzheimer's disease; Amyloid beta; Animal models; GSK-3 beta; Neurodegeneration; Tau protein.
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