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

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. G...

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Autores principales: Sayas, Carmen Laura, Ávila, Jesús
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063930/
https://www.ncbi.nlm.nih.gov/pubmed/33804962
http://dx.doi.org/10.3390/cells10040721
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author Sayas, Carmen Laura
Ávila, Jesús
author_facet Sayas, Carmen Laura
Ávila, Jesús
author_sort Sayas, Carmen Laura
collection PubMed
description 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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spelling pubmed-80639302021-04-24 GSK-3 and Tau: A Key Duet in Alzheimer’s Disease Sayas, Carmen Laura Ávila, Jesús Cells Review 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. MDPI 2021-03-24 /pmc/articles/PMC8063930/ /pubmed/33804962 http://dx.doi.org/10.3390/cells10040721 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Review
Sayas, Carmen Laura
Ávila, Jesús
GSK-3 and Tau: A Key Duet in Alzheimer’s Disease
title GSK-3 and Tau: A Key Duet in Alzheimer’s Disease
title_full GSK-3 and Tau: A Key Duet in Alzheimer’s Disease
title_fullStr GSK-3 and Tau: A Key Duet in Alzheimer’s Disease
title_full_unstemmed GSK-3 and Tau: A Key Duet in Alzheimer’s Disease
title_short GSK-3 and Tau: A Key Duet in Alzheimer’s Disease
title_sort gsk-3 and tau: a key duet in alzheimer’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063930/
https://www.ncbi.nlm.nih.gov/pubmed/33804962
http://dx.doi.org/10.3390/cells10040721
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