The pleiotropic roles of autophagy in Alzheimer's disease: From pathophysiology to therapy.


Journal

Current opinion in pharmacology
ISSN: 1471-4973
Titre abrégé: Curr Opin Pharmacol
Pays: England
ID NLM: 100966133

Informations de publication

Date de publication:
10 2021
Historique:
received: 25 06 2021
accepted: 19 07 2021
pubmed: 23 8 2021
medline: 9 11 2021
entrez: 22 8 2021
Statut: ppublish

Résumé

Autophagy is a lysosomal degradation pathway and the main clearance route of many toxic protein aggregates. The molecular pathology of Alzheimer's disease (AD) manifests in the form of protein aggregates-extracellular amyloid-β depositions and intracellular tau neurofibrillary tangles. Perturbations at different steps of the autophagy pathway observed in cellular and animal models of AD might contribute to amyloid-β and tau accumulation. Increased levels of autophagosomes detected in patients' brains suggest an alteration of autophagy in human disease. Autophagy is also involved in the fine-tuning of inflammation, which increases in the early stages of AD and possibly drives its pathogenesis. Mounting evidence of a causal link between impaired autophagy and AD pathology uncovers an exciting opportunity for the development of autophagy-based therapeutics.

Identifiants

pubmed: 34419832
pii: S1471-4892(21)00105-3
doi: 10.1016/j.coph.2021.07.011
pmc: PMC8519395
pii:
doi:

Substances chimiques

Amyloid beta-Peptides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

149-157

Subventions

Organisme : Medical Research Council
ID : UKDRI-2002
Pays : United Kingdom

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

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Auteurs

Beatrice Paola Festa (BP)

Department of Medical Genetics, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK; UK Dementia Research Institute, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK.

Antonio Daniel Barbosa (AD)

Department of Medical Genetics, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK; UK Dementia Research Institute, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK.

Matea Rob (M)

Department of Medical Genetics, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK; UK Dementia Research Institute, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK.

David C Rubinsztein (DC)

Department of Medical Genetics, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK; UK Dementia Research Institute, Cambridge Institute for Medical Research (CIMR), University of Cambridge, Cambridge, UK. Electronic address: dcr1000@cam.ac.uk.

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Classifications MeSH