Role of GSK-3β in Alzheimer's disease pathology

Glycogen synthase kinase 3beta (GSK-3beta) is an important regulatory kinase involved in multiple processes such as metabolic control, embryonic development, cell death, and oncogenesis. It has been found to interact with many molecules associated with Alzheimer's disease (AD) such as the microtubule-associated protein tau, presenilin 1, the amyloid-beta peptide, the amyloid precursor protein, and acetylcholine. Furthermore, GSK-3beta might be involved in brain aging and longevity. As GSK-3beta is associated with so many components of AD pathology, we review the current data on the role of this kinase in tau hyperphosphorylation, then look at its association with AD-related molecules and pathways, and finally discuss its involvement in cell death and aging. We attempt to integrate all these data to arrive at the proposition that GSK-3beta is a pivotal molecule in the evolution of AD and that developing drugs directed at this kinase might prove to be beneficial in the treatment of this devastating disease.