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Chakravorty A, Jetto CT, Manjithaya R. Dysfunctional Mitochondria and Mitophagy as Drivers of Alzheimer's Disease Pathogenesis. Front Aging Neurosci. 2019;11:311doi: 10.3389/fnagi.2019.00311.
Chakravorty, A., Jetto, C. T., & Manjithaya, R. (2019). Dysfunctional Mitochondria and Mitophagy as Drivers of Alzheimer's Disease Pathogenesis. Frontiers in aging neuroscience, 11311. https://doi.org/10.3389/fnagi.2019.00311
Chakravorty, Anushka, et al. "Dysfunctional Mitochondria and Mitophagy as Drivers of Alzheimer's Disease Pathogenesis." Frontiers in aging neuroscience vol. 11 (2019): 311. doi: https://doi.org/10.3389/fnagi.2019.00311
Chakravorty A, Jetto CT, Manjithaya R. Dysfunctional Mitochondria and Mitophagy as Drivers of Alzheimer's Disease Pathogenesis. Front Aging Neurosci. 2019 Nov 20;11:311. doi: 10.3389/fnagi.2019.00311. eCollection 2019. PMID: 31824296; PMCID: PMC6880761.
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Front Aging Neurosci. 2019 Nov 20;11:311. doi: 10.3389/fnagi.2019.00311. eCollection 2019.

Dysfunctional Mitochondria and Mitophagy as Drivers of Alzheimer's Disease Pathogenesis.

Frontiers in aging neuroscience

Anushka Chakravorty, Cuckoo Teresa Jetto, Ravi Manjithaya

Affiliations

  1. Autophagy Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, India.
  2. Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, India.

PMID: 31824296 PMCID: PMC6880761 DOI: 10.3389/fnagi.2019.00311

Abstract

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.

Copyright © 2019 Chakravorty, Jetto and Manjithaya.

Keywords: Alzheimer’s disease; amyloid beta; microglia; mitochondrial dysfunction; mitophagy; tau

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