Glycogen Synthase Kinase-3 (GSK-3) Inhibitors for the Treatment of Alzheimers Disease

Miguel      Medina; Jesus      Avila

Abstract

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 Alzheimers disease (AD) pathology. Besides having been identified as the major tau protein kinase, GSK-3 mediates Aβ neurotoxicity, plays an essential role in synaptic plasticity and memory, might be involved in Aβ 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.

Keywords: GSK-3, Alzheimer's disease, Tau, amyloid, neurodegeneration, lithium, memory, neuroinflammation