GSK-3 and Tau: A Key Duet in Alzheimer's Disease.

Cells

Centro de Biología Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Científicas (CSIC) y la Universidad Autónoma de Madrid (UAM), 28049 Madrid, Spain.

Published: March 2021

Glycogen synthase kinase-3 (GSK-3) is a ubiquitously expressed serine/threonine kinase with a plethora of substrates. As a modulator of several cellular processes, GSK-3 has a central position in cell metabolism and signaling, with important roles both in physiological and pathological conditions. GSK-3 has been associated with a number of human disorders, such as neurodegenerative diseases including Alzheimer's disease (AD). GSK-3 contributes to the hyperphosphorylation of tau protein, the main component of neurofibrillary tangles (NFTs), one of the hallmarks of AD. GSK-3 is further involved in the regulation of different neuronal processes that are dysregulated during AD pathogenesis, such as the generation of amyloid-β (Aβ) peptide or Aβ-induced cell death, axonal transport, cholinergic function, and adult neurogenesis or synaptic function. In this review, we will summarize recent data about GSK-3 involvement in these processes contributing to AD pathology, mostly focusing on the crucial interplay between GSK-3 and tau protein. We further discuss the current development of potential AD therapies targeting GSK-3 or GSK-3-phosphorylated tau.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063930PMC
http://dx.doi.org/10.3390/cells10040721DOI Listing

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