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. 2022;20(4):675-692.
doi: 10.2174/1570159X19666210517114016.

Mitochondrial Dysfunction in Alzheimer's Disease: Opportunities for Drug Development

Shiveena Bhatia  1 , Rishi Rawal  2 , Pratibha Sharma  1 , Tanveer Singh  3 , Manjinder Singh  1 , Varinder Singh  1
Affiliations

Mitochondrial Dysfunction in Alzheimer's Disease: Opportunities for Drug Development

Shiveena Bhatia et al. Curr Neuropharmacol. 2022.

Abstract

Alzheimer's disease (AD) is one of the major reasons for 60-80% cases of senile dementia occurring as a result of the accumulation of plaques and tangles in the hippocampal and cortical neurons of the brain leading to neurodegeneration and cell death. The other pathological features of AD comprise abnormal microvasculature, network abnormalities, interneuronal dysfunction, increased β-amyloid production and reduced clearance, increased inflammatory response, elevated production of reactive oxygen species, impaired brain metabolism, hyperphosphorylation of tau, and disruption of acetylcholine signaling. Among all these pathologies, Mitochondrial Dysfunction (MD), regardless of it being an inciting insult or a consequence of the alterations, is related to all the associated AD pathologies. Observed altered mitochondrial morphology, distribution and movement, increased oxidative stress, dysregulation of enzymes involved in mitochondrial functioning, impaired brain metabolism, and impaired mitochondrial biogenesis in AD subjects suggest the involvement of mitochondrial malfunction in the progression of AD. Here, various pre-clinical and clinical evidence establishing MD as a key mediator in the progression of neurodegeneration in AD are reviewed and discussed with an aim to foster future MD based drug development research for the management of AD.

Keywords: Alzheimer’s disease; apoptosis; mitochondrial dysfunction; oxidative stress; tau proteins; β-amyloid plaques.

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Figures

Fig. (1)
Fig. (1)
Role of calcium signalling in mitochondrial dysfunction mediated neuronal apoptosis.
Fig. (2)
Fig. (2)
Mechanisms involving caspase dependent neuronal apoptosis.
Fig. (3)
Fig. (3)
Interplay between mitochondrial dysfunction and classical theories of Alzheimer’s disease.
See this image and copyright information in PMC

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