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Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease

Alzheimer's disease (AD) is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disea...

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Autor principal: Onyango, Isaac G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840984/
https://www.ncbi.nlm.nih.gov/pubmed/29451200
http://dx.doi.org/10.4103/1673-5374.224362
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author Onyango, Isaac G.
author_facet Onyango, Isaac G.
author_sort Onyango, Isaac G.
collection PubMed
description Alzheimer's disease (AD) is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.
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spelling pubmed-58409842018-03-12 Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease Onyango, Isaac G. Neural Regen Res Invited Review Alzheimer's disease (AD) is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria. Medknow Publications & Media Pvt Ltd 2018-01 /pmc/articles/PMC5840984/ /pubmed/29451200 http://dx.doi.org/10.4103/1673-5374.224362 Text en Copyright: © Neural Regeneration Research http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Invited Review
Onyango, Isaac G.
Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease
title Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease
title_full Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease
title_fullStr Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease
title_full_unstemmed Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease
title_short Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease
title_sort modulation of mitochondrial bioenergetics as a therapeutic strategy in alzheimer's disease
topic Invited Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840984/
https://www.ncbi.nlm.nih.gov/pubmed/29451200
http://dx.doi.org/10.4103/1673-5374.224362
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