Dysfunctional Mitochondria and Mitophagy as Drivers of Alzheimer's Disease Pathogenesis.
Alzheimer’s disease
amyloid beta
microglia
mitochondrial dysfunction
mitophagy
tau
Journal
Frontiers in aging neuroscience
ISSN: 1663-4365
Titre abrégé: Front Aging Neurosci
Pays: Switzerland
ID NLM: 101525824
Informations de publication
Date de publication:
2019
2019
Historique:
received:
13
09
2019
accepted:
28
10
2019
entrez:
12
12
2019
pubmed:
12
12
2019
medline:
12
12
2019
Statut:
epublish
Résumé
Neurons are highly specialized post-mitotic cells that are inherently dependent on mitochondria owing to their high bioenergetic demand. Mitochondrial dysfunction is therefore associated with various age-related neurodegenerative disorders such as Alzheimer's disease (AD), wherein accumulation of damaged and dysfunctional mitochondria has been reported as an early symptom further contributing to disease progression. In AD, impairment of mitochondrial function causes bioenergetic deficiency, intracellular calcium imbalance and oxidative stress, thereby aggravating the effect of Aβ and tau pathologies, leading to synaptic dysfunction, cognitive impairment and memory loss. Although there are reports suggesting intricate parallelism between mitochondrial dysfunction and AD pathologies such as Aβ aggregation and hyperphosphorylated tau accumulation, the factors that drive the pathogenesis of either are unclear. In addition, emerging evidence suggest that mitochondrial quality control (QC) mechanisms such as mitophagy are impaired in AD. As an important mitochondrial QC mechanism, mitophagy plays a critical role in maintaining neuronal health and function. Studies show that various proteins involved in mitophagy, mitochondrial dynamics, and mitochondrial biogenesis are affected in AD. Compromised mitophagy may also be attributed to impairment in autophagosome-lysosome fusion and defects in lysosomal acidification. Therapeutic interventions aiming to restore mitophagy functions can be used as a strategy for ameliorating AD pathogenesis. Recent evidence implicates the role of microglial activation via mitophagy induction in reducing amyloid plaque load. This review summarizes the current developments in the field of mitophagy and mitochondrial dysfunction in AD.
Identifiants
pubmed: 31824296
doi: 10.3389/fnagi.2019.00311
pmc: PMC6880761
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
311Informations de copyright
Copyright © 2019 Chakravorty, Jetto and Manjithaya.
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