Cargando…

Mitochondrial Regulation of Microglial Immunometabolism in Alzheimer’s Disease

Alzheimer’s disease (AD) is an age-associated terminal neurodegenerative disease with no effective treatments. Dysfunction of innate immunity is implicated in the pathogenesis of AD, with genetic studies supporting a causative role in the disease. Microglia, the effector cells of innate immunity in...

Descripción completa

Detalles Bibliográficos
Autores principales: Fairley, Lauren H., Wong, Jia Hui, Barron, Anna M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947196/
https://www.ncbi.nlm.nih.gov/pubmed/33717134
http://dx.doi.org/10.3389/fimmu.2021.624538
_version_ 1783663171147399168
author Fairley, Lauren H.
Wong, Jia Hui
Barron, Anna M.
author_facet Fairley, Lauren H.
Wong, Jia Hui
Barron, Anna M.
author_sort Fairley, Lauren H.
collection PubMed
description Alzheimer’s disease (AD) is an age-associated terminal neurodegenerative disease with no effective treatments. Dysfunction of innate immunity is implicated in the pathogenesis of AD, with genetic studies supporting a causative role in the disease. Microglia, the effector cells of innate immunity in the brain, are highly plastic and perform a diverse range of specialist functions in AD, including phagocytosing and removing toxic aggregates of beta amyloid and tau that drive neurodegeneration. These immune functions require high energy demand, which is regulated by mitochondria. Reflecting this, microglia have been shown to be highly metabolically flexible, reprogramming their mitochondrial function upon inflammatory activation to meet their energy demands. However, AD-associated genetic risk factors and pathology impair microglial metabolic programming, and metabolic derailment has been shown to cause innate immune dysfunction in AD. These findings suggest that immunity and metabolic function are intricately linked processes, and targeting microglial metabolism offers a window of opportunity for therapeutic treatment of AD. Here, we review evidence for the role of metabolic programming in inflammatory functions in AD, and discuss mitochondrial-targeted immunotherapeutics for treatment of the disease.
format Online
Article
Text
id pubmed-7947196
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-79471962021-03-12 Mitochondrial Regulation of Microglial Immunometabolism in Alzheimer’s Disease Fairley, Lauren H. Wong, Jia Hui Barron, Anna M. Front Immunol Immunology Alzheimer’s disease (AD) is an age-associated terminal neurodegenerative disease with no effective treatments. Dysfunction of innate immunity is implicated in the pathogenesis of AD, with genetic studies supporting a causative role in the disease. Microglia, the effector cells of innate immunity in the brain, are highly plastic and perform a diverse range of specialist functions in AD, including phagocytosing and removing toxic aggregates of beta amyloid and tau that drive neurodegeneration. These immune functions require high energy demand, which is regulated by mitochondria. Reflecting this, microglia have been shown to be highly metabolically flexible, reprogramming their mitochondrial function upon inflammatory activation to meet their energy demands. However, AD-associated genetic risk factors and pathology impair microglial metabolic programming, and metabolic derailment has been shown to cause innate immune dysfunction in AD. These findings suggest that immunity and metabolic function are intricately linked processes, and targeting microglial metabolism offers a window of opportunity for therapeutic treatment of AD. Here, we review evidence for the role of metabolic programming in inflammatory functions in AD, and discuss mitochondrial-targeted immunotherapeutics for treatment of the disease. Frontiers Media S.A. 2021-02-25 /pmc/articles/PMC7947196/ /pubmed/33717134 http://dx.doi.org/10.3389/fimmu.2021.624538 Text en Copyright © 2021 Fairley, Wong and Barron http://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 Immunology
Fairley, Lauren H.
Wong, Jia Hui
Barron, Anna M.
Mitochondrial Regulation of Microglial Immunometabolism in Alzheimer’s Disease
title Mitochondrial Regulation of Microglial Immunometabolism in Alzheimer’s Disease
title_full Mitochondrial Regulation of Microglial Immunometabolism in Alzheimer’s Disease
title_fullStr Mitochondrial Regulation of Microglial Immunometabolism in Alzheimer’s Disease
title_full_unstemmed Mitochondrial Regulation of Microglial Immunometabolism in Alzheimer’s Disease
title_short Mitochondrial Regulation of Microglial Immunometabolism in Alzheimer’s Disease
title_sort mitochondrial regulation of microglial immunometabolism in alzheimer’s disease
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947196/
https://www.ncbi.nlm.nih.gov/pubmed/33717134
http://dx.doi.org/10.3389/fimmu.2021.624538
work_keys_str_mv AT fairleylaurenh mitochondrialregulationofmicroglialimmunometabolisminalzheimersdisease
AT wongjiahui mitochondrialregulationofmicroglialimmunometabolisminalzheimersdisease
AT barronannam mitochondrialregulationofmicroglialimmunometabolisminalzheimersdisease