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Plausible Role of Mitochondrial DNA Copy Number in Neurodegeneration—a Need for Therapeutic Approach in Parkinson’s Disease (PD)

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Abstract

Parkinson’s disease (PD) is an advancing age-associated progressive brain disorder which has various diverse factors, among them mitochondrial dysfunction involves in dopaminergic (DA) degeneration. Aging causes a rise in mitochondrial abnormalities which leads to structural and functional modifications in neuronal activity and cell death in PD. This ends in deterioration of mitochondrial function, mitochondrial alterations, mitochondrial DNA copy number (mtDNA CN) and oxidative phosphorylation (OXPHOS) capacity. mtDNA levels or mtDNA CN in PD have reported that mtDNA depletion would be a predisposing factor in PD pathogenesis. To maintain the mtDNA levels, therapeutic approaches have been focused on mitochondrial biogenesis in PD. The depletion of mtDNA levels in PD can be influenced by autophagic dysregulation, apoptosis, neuroinflammation, oxidative stress, sirtuins, and calcium homeostasis. The current review describes the regulation of mtDNA levels and discusses the plausible molecular pathways in mtDNA CN depletion in PD pathogenesis. We conclude by suggesting further research on mtDNA depletion which might show a promising effect in predicting and diagnosing PD.

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Funding

This work was supported by the Indian Council of Medical Research DHR-GIA [grant number: GIA/2019/000276/PRCGIA], Government of India.

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Authors and Affiliations

  1. Centre for Neuroscience, Department of Biotechnology, Karpagam Academy of Higher Education (Deemed to Be University), Coimbatore, 641021, India

    Dhivya Venkatesan & Mahalaxmi Iyer

  2. Disease Proteomics Laboratory, Department of Zoology, Bharathiar University, Coimbatore, 641046, Tamil Nadu, India

    Arul Narayanasamy

  3. Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology, Tamil Nadu, Vellore, 632014, India

    Abilash Valsala Gopalakrishnan

  4. Cytogenetics and Stem Cell Laboratory, Department of Zoology, School of Basic Sciences, Central University of Punjab, Bathinda, Punjab, 151401, India

    Balachandar Vellingiri

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  1. Dhivya Venkatesan
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  4. Abilash Valsala Gopalakrishnan
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Contributions

Balachanar Vellingri and Dhivya Venkatesan contributed to conceptualization of the review. Writing—original draft was performed by Dhivya Venkatesan and Mahalaxmi Iyer. Reviewing and final approval of the article was approved by Arul Narayanasamy, Abilash Valsala Gopalakrishnan, and Balachandar Vellingiri.

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Venkatesan, D., Iyer, M., Narayanasamy, A. et al. Plausible Role of Mitochondrial DNA Copy Number in Neurodegeneration—a Need for Therapeutic Approach in Parkinson’s Disease (PD). Mol Neurobiol 60, 6992–7008 (2023). https://doi.org/10.1007/s12035-023-03500-x

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