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Mitochondrial Dysfunction: A Key Player in the Pathogenesis of Autism Spectrum Disorders and Alzheimer’s Disease

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Autism Spectrum Disorder and Alzheimer's Disease

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Abstract

Increasing evidence has pinpointed that loss of mitochondrial function or regulation is a critical player toward the pathogenesis of various metabolic, neurodevelopmental, and neurodegenerative disorders, including autism spectrum disorders (ASD) and Alzheimer’s disease (AD). The lacuna in understanding these diseases’ underlying biology is that pathology develops through the interaction of various biological pathways rather than a defined mechanism. Mitochondria are dynamic organelles that perform diverse functions, including cellular energy production, calcium homeostasis, apoptosis, and innate immune regulation. Hence, mitochondria integrate various cellular pathways, and any exogenous or endogenous perturbation may result in their dysfunction. Herein, we explore the latest research insights that have evolved our understanding of ASD and AD pathogenesis with the perspective of mitochondrial dysregulation as the underlying phenomenon. We discuss the pathological relevance of cause and effect of mitochondrial dysregulation, such as increased reactive oxygen species (ROS) production, mitochondrial DNA damage, aberrant immune responses, impaired energy metabolism, and altered gut microbiome in the etiology of ASD and AD. Being at the center stage, mitochondria have emerged as a novel target with considerable therapeutic potential, which can be exploited to delay, manage, or treat ASD, AD, and other neurological disorders. We also discuss the novel therapeutic options such as H2S therapy, dynamic microbiome modulation, ketogenic diet, and cofactor therapy that are emerging as a plausible treatment regimen and have shown favorable outcomes in initial studies. Hence, this article summarizes the current understanding of the functional and structural disturbances in the mitochondria that lead to ASD and AD and could be harnessed for better diagnostic and prognostic outcomes.

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Authors and Affiliations

  1. Department of Clinical Laboratory Sciences, College of Applied Medical Science, Jouf University, Sakaka, Saudi Arabia

    Aisha Farhana

  2. Basic Sciences Department, College of Medicine, Vision (Al Farabi) Colleges, Riyadh, Saudi Arabia

    Yusuf Saleem Khan

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  1. Aisha Farhana
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  1. King Fahd Medical Research Center Department of Medical Laboratory Sciences Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

    Ghulam Md Ashraf

  2. Department of Science and Engineering, Novel Global Community Educational Foundation, Sydney, Australia

    Athanasios Alexiou

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Farhana, A., Khan, Y.S. (2021). Mitochondrial Dysfunction: A Key Player in the Pathogenesis of Autism Spectrum Disorders and Alzheimer’s Disease. In: Md Ashraf, G., Alexiou, A. (eds) Autism Spectrum Disorder and Alzheimer's Disease . Springer, Singapore. https://doi.org/10.1007/978-981-16-4558-7_2

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