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The emerging role of autophagy and mitophagy in tauopathies: From pathogenesis to translational implications in Alzheimer’s disease

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, affecting more than 55 million individuals worldwide in 2021. In addition to the “amyloid hypothesis,” an increasing number of studies have demonstrated that phosphorylated tau plays an important role in AD pathogenesis. Both...

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Autores principales: Liu, Xiaolan, Ye, Meng, Ma, Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618726/
https://www.ncbi.nlm.nih.gov/pubmed/36325189
http://dx.doi.org/10.3389/fnagi.2022.1022821
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author Liu, Xiaolan
Ye, Meng
Ma, Liang
author_facet Liu, Xiaolan
Ye, Meng
Ma, Liang
author_sort Liu, Xiaolan
collection PubMed
description Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, affecting more than 55 million individuals worldwide in 2021. In addition to the “amyloid hypothesis,” an increasing number of studies have demonstrated that phosphorylated tau plays an important role in AD pathogenesis. Both soluble tau oligomers and insoluble tau aggregates in the brain can induce structural and functional neuronal damage through multiple pathways, eventually leading to memory deficits and neurodegeneration. Autophagy is an important cellular response to various stress stimuli and can generally be categorized into non-selective and selective autophagy. Recent studies have indicated that both types of autophagy are involved in AD pathology. Among the several subtypes of selective autophagy, mitophagy, which mediates the selective removal of mitochondria, has attracted increasing attention because dysfunctional mitochondria have been suggested to contribute to tauopathies. In this review, we summarize the latest findings on the bidirectional association between abnormal tau proteins and defective autophagy, as well as mitophagy, which might constitute a vicious cycle in the induction of neurodegeneration. Neuroinflammation, another important feature in the pathogenesis and progression of AD, has been shown to crosstalk with autophagy and mitophagy. Additionally, we comprehensively discuss the relationship between neuroinflammation, autophagy, and mitophagy. By elucidating the underlying molecular mechanisms governing these pathologies, we highlight novel therapeutic strategies targeting autophagy, mitophagy and neuroinflammation, such as those using rapamycin, urolithin, spermidine, curcumin, nicotinamide, and actinonin, for the prevention and treatment of AD.
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spelling pubmed-96187262022-11-01 The emerging role of autophagy and mitophagy in tauopathies: From pathogenesis to translational implications in Alzheimer’s disease Liu, Xiaolan Ye, Meng Ma, Liang Front Aging Neurosci Neuroscience Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, affecting more than 55 million individuals worldwide in 2021. In addition to the “amyloid hypothesis,” an increasing number of studies have demonstrated that phosphorylated tau plays an important role in AD pathogenesis. Both soluble tau oligomers and insoluble tau aggregates in the brain can induce structural and functional neuronal damage through multiple pathways, eventually leading to memory deficits and neurodegeneration. Autophagy is an important cellular response to various stress stimuli and can generally be categorized into non-selective and selective autophagy. Recent studies have indicated that both types of autophagy are involved in AD pathology. Among the several subtypes of selective autophagy, mitophagy, which mediates the selective removal of mitochondria, has attracted increasing attention because dysfunctional mitochondria have been suggested to contribute to tauopathies. In this review, we summarize the latest findings on the bidirectional association between abnormal tau proteins and defective autophagy, as well as mitophagy, which might constitute a vicious cycle in the induction of neurodegeneration. Neuroinflammation, another important feature in the pathogenesis and progression of AD, has been shown to crosstalk with autophagy and mitophagy. Additionally, we comprehensively discuss the relationship between neuroinflammation, autophagy, and mitophagy. By elucidating the underlying molecular mechanisms governing these pathologies, we highlight novel therapeutic strategies targeting autophagy, mitophagy and neuroinflammation, such as those using rapamycin, urolithin, spermidine, curcumin, nicotinamide, and actinonin, for the prevention and treatment of AD. Frontiers Media S.A. 2022-10-17 /pmc/articles/PMC9618726/ /pubmed/36325189 http://dx.doi.org/10.3389/fnagi.2022.1022821 Text en Copyright © 2022 Liu, Ye and Ma. https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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.
spellingShingle Neuroscience
Liu, Xiaolan
Ye, Meng
Ma, Liang
The emerging role of autophagy and mitophagy in tauopathies: From pathogenesis to translational implications in Alzheimer’s disease
title The emerging role of autophagy and mitophagy in tauopathies: From pathogenesis to translational implications in Alzheimer’s disease
title_full The emerging role of autophagy and mitophagy in tauopathies: From pathogenesis to translational implications in Alzheimer’s disease
title_fullStr The emerging role of autophagy and mitophagy in tauopathies: From pathogenesis to translational implications in Alzheimer’s disease
title_full_unstemmed The emerging role of autophagy and mitophagy in tauopathies: From pathogenesis to translational implications in Alzheimer’s disease
title_short The emerging role of autophagy and mitophagy in tauopathies: From pathogenesis to translational implications in Alzheimer’s disease
title_sort emerging role of autophagy and mitophagy in tauopathies: from pathogenesis to translational implications in alzheimer’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618726/
https://www.ncbi.nlm.nih.gov/pubmed/36325189
http://dx.doi.org/10.3389/fnagi.2022.1022821
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