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Mitochondrial Dysfunction and Mitophagy Closely Cooperate in Neurological Deficits Associated with Alzheimer’s Disease and Type 2 Diabetes

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Abstract

Alzheimer’s disease (AD) and type 2 diabetes (T2D) are known to be correlated in terms of their epidemiology, histopathology, and molecular and biochemical characteristics. The prevalence of T2D leading to AD is approximately 50–70%. Moreover, AD is often considered type III diabetes because of the common risk factors. Uncontrolled T2D may affect the brain, leading to memory and learning deficits in patients. In addition, metabolic disorders and impaired oxidative phosphorylation in AD and T2D patients suggest that mitochondrial dysfunction is involved in both diseases. The dysregulation of pathways involved in maintaining mitochondrial dynamics, biogenesis and mitophagy are responsible for exacerbating the impact of hyperglycemia on the brain and neurodegeneration under T2D conditions. The first section of this review describes the recent views on mitochondrial dysfunction that connect these two disease conditions, as the pathways are observed to overlap. The second section of the review highlights the importance of different mitochondrial miRNAs (mitomiRs) involved in the regulation of mitochondrial dynamics and their association with the pathogenesis of T2D and AD. Therefore, targeting mitochondrial biogenesis and mitophagy pathways, along with the use of mitomiRs, could be a potent therapeutic strategy for T2D-related AD. The last section of the review highlights the known drugs targeting mitochondrial function for the treatment of both disease conditions.

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We acknowledge the Council of Scientific & Industrial Research (CSIR), India and Science and Engineering Research Board (SERB), India for funding this work. SP acknowledges a junior research fellowship from UGC

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  1. Sangita Paul and Debarpita Saha have contributed equally to this work

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  1. CSIR-Institute of Genomics and Integrative Biology, Delhi, India

    Sangita Paul, Debarpita Saha & Binukumar BK

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

    Sangita Paul & Binukumar BK

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BK conceived the original idea and designed the outlines of the study. SP and DS wrote the draft of the manuscript. SP and DS prepared the figures for the manuscript. SP and DS performed the literature review. SP aided in revising the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Binukumar BK.

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Paul, S., Saha, D. & BK, B. Mitochondrial Dysfunction and Mitophagy Closely Cooperate in Neurological Deficits Associated with Alzheimer’s Disease and Type 2 Diabetes. Mol Neurobiol 58, 3677–3691 (2021). https://doi.org/10.1007/s12035-021-02365-2

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