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Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease

Alzheimer's disease (AD) is characterized by the accumulation of misfolded amyloid-beta and tau proteins. Autophagy acts as a proteostasis process to remove protein clumps, although it progressively weakens with aging and AD, thus facilitating the accumulation of toxic proteins and causing neur...

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Autores principales: Barmaki, Haleh, Nourazarian, Alireza, Khaki-Khatibi, Fatemeh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652403/
https://www.ncbi.nlm.nih.gov/pubmed/38020769
http://dx.doi.org/10.3389/fnagi.2023.1281338
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author Barmaki, Haleh
Nourazarian, Alireza
Khaki-Khatibi, Fatemeh
author_facet Barmaki, Haleh
Nourazarian, Alireza
Khaki-Khatibi, Fatemeh
author_sort Barmaki, Haleh
collection PubMed
description Alzheimer's disease (AD) is characterized by the accumulation of misfolded amyloid-beta and tau proteins. Autophagy acts as a proteostasis process to remove protein clumps, although it progressively weakens with aging and AD, thus facilitating the accumulation of toxic proteins and causing neurodegeneration. This review examines the impact of impaired autophagy on the progression of AD disease pathology. Under normal circumstances, autophagy removes abnormal proteins and damaged organelles, but any dysfunction in this process can lead to the exacerbation of amyloid and tau pathology, particularly in AD. There is increasing attention to therapeutic tactics to revitalize autophagy, including reduced caloric intake, autophagy-stimulating drugs, and genetic therapy. However, the translation of these strategies into clinical practice faces several hurdles. In summary, this review integrates the understanding of the intricate role of autophagy dysfunction in Alzheimer's disease progression and reinforces the promising prospects of autophagy as a beneficial target for treatments to modify the course of Alzheimer's disease.
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spelling pubmed-106524032023-01-01 Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease Barmaki, Haleh Nourazarian, Alireza Khaki-Khatibi, Fatemeh Front Aging Neurosci Aging Neuroscience Alzheimer's disease (AD) is characterized by the accumulation of misfolded amyloid-beta and tau proteins. Autophagy acts as a proteostasis process to remove protein clumps, although it progressively weakens with aging and AD, thus facilitating the accumulation of toxic proteins and causing neurodegeneration. This review examines the impact of impaired autophagy on the progression of AD disease pathology. Under normal circumstances, autophagy removes abnormal proteins and damaged organelles, but any dysfunction in this process can lead to the exacerbation of amyloid and tau pathology, particularly in AD. There is increasing attention to therapeutic tactics to revitalize autophagy, including reduced caloric intake, autophagy-stimulating drugs, and genetic therapy. However, the translation of these strategies into clinical practice faces several hurdles. In summary, this review integrates the understanding of the intricate role of autophagy dysfunction in Alzheimer's disease progression and reinforces the promising prospects of autophagy as a beneficial target for treatments to modify the course of Alzheimer's disease. Frontiers Media S.A. 2023-11-02 /pmc/articles/PMC10652403/ /pubmed/38020769 http://dx.doi.org/10.3389/fnagi.2023.1281338 Text en Copyright © 2023 Barmaki, Nourazarian and Khaki-Khatibi. 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 Aging Neuroscience
Barmaki, Haleh
Nourazarian, Alireza
Khaki-Khatibi, Fatemeh
Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease
title Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease
title_full Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease
title_fullStr Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease
title_full_unstemmed Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease
title_short Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease
title_sort proteostasis and neurodegeneration: a closer look at autophagy in alzheimer's disease
topic Aging Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652403/
https://www.ncbi.nlm.nih.gov/pubmed/38020769
http://dx.doi.org/10.3389/fnagi.2023.1281338
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