GSK3B

Phosphorylation

Internal medicine

Neuroscience

GSK-3

Kinase

Glycogen synthase

Tau protein

Disease

Dementia

Neuropathology

Neurogenesis

Alzheimer's disease

Bioinformatics

Medicine

Biology

Cell biology

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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. • GSK3-β kinase increases with age and in AD pathology. • GSK3-β dysregulation modulates Aβ production and accumulation in AD. • Hyperactive GSK3-β promotes phosphorylation and formation of toxic tau species. • GSK3-β activation is pro-inflammatory and impairs LTP, neurogenesis and memory. • GSK3-β represents a good therapeutic target against AD.

Glycogen synthase kinase-3 signaling in Alzheimer's disease