REVIEW article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Volume 19 - 2025 | doi: 10.3389/fncel.2025.1650400
This article is part of the Research TopicImpacts of cytoskeletal dysregulation on spinogenesisView all 3 articles
The role of small GTPases in Alzheimer's disease tau pathologies
Provisionally accepted
- University of South Carolina, Columbia, United States
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Abstract Microtubule-associated protein (MAP) tau stabilizes neuronal microtubules in axonal transport and contributes to healthy synapses. In Alzheimer's disease (AD), tau proteins become hyperphosphorylated, reduce microtubule binding, and aggregate into paired helical filaments (PHFs) in neurofibrillary tangles (NFTs). Although the steps of this dysregulation of tau are well established, the mechanisms by which each step is regulated remain incompletely understood. Misfolded protein aggregates, such as amyloid β-peptides (Aβ), are degraded by autophagy and lysosomal pathways, in which small GTPases play essential roles. However, how tau aggregates and spreads from nerve cells and whether small GTPases similarly play pivotal roles are not as clear. Here we review the recent evidence to propose that small GTPases are important in tau protein posttranslational phosphorylation, aggregation, and clearance. As such, small GTPases may prove to be important therapeutic targets that can reduce the AD tau burden.
Keywords: Alzheimer's disease, small GTPases, microtubule-associated protein tau, hyperphosphorylation, Aggregation, propagation, Clearance, Neurofibrillary Tangles
Received: 19 Jun 2025; Accepted: 29 Aug 2025.
Copyright: © 2025 Hoegy, Chen and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qun Lu, University of South Carolina, Columbia, United States
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