Glycogen Synthase Kinase-3 (GSK-3) Inhibitors for the Treatment of Alzheimer's Disease

Originally discovered because of its role in the regulation of glucose metabolism, Glycogen Synthase Kinase-3 (GSK-3) is now recognised as a crucial player in a diverse series of cellular processes involved in Alzheimer's disease (AD) pathology. Besides having been identified as the major tau protein kinase, GSK-3 mediates A beta neurotoxicity, plays an essential role in synaptic plasticity and memory, might be involved in A beta formation, and it has an important role in inflammation and neuronal survival, all key features of AD neuropathology. Moreover, AD was one of the earliest disorders linked to GSK-3 dysfunction. Thus, the discovery of small molecule GSK-3 inhibitors has attracted significant attention to the protein both as for the therapeutic intervention in neurodegenerative diseases as well as a means to understand the molecular basis of these disorders.