Abstract
Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of the α-synuclein aggregates. Among the proposed pathogenic mechanisms, mitochondrial dysfunction plays a central role, contributing to bioenergetic failure, oxidative stress, and neuronal death. This article explores the mechanisms of mitochondrial impairment in PD, with a focus on genetic factors (PINK1, Parkin, LRRK2), mitophagy failure, and oxidative damage. Furthermore, it highlights current and emerging precision therapeutic strategies targeting mitochondrial health, including antioxidants, mitophagy inducers, and gene therapies. Targeting mitochondrial pathways presents a promising direction for disease modification and neuroprotection in Parkinson’s Disease.
References
Bose, A., & Beal, M. F. (2016). Mitochondrial dysfunction in Parkinson’s disease.
Journal of Neurochemistry, 139(1), 216–231. https://doi.org/10.1111/jnc.13731
Exner, N., Lutz, A. K., Haass, C., & Winklhofer, K. F. (2012). Mitochondrial dysfunction in Parkinson's disease: Molecular mechanisms and pathophysiological consequences. The EMBO Journal, 31(14), 3038–3062. https://doi.org/10.1038/emboj.2012.170
Grünewald, A., Kumar Krishnan, K. J., & Turnbull, D. M. (2019). Mitochondrial dysfunction in Parkinson's disease: A pathophysiological link to clinical features. Movement Disorders, 34(9), 1347–1356. https://doi.org/10.1002/mds.27889
Ryan, B. J., Hoek, S., Fon, E. A., & Wade-Martins, R. (2015). Mitochondrial dysfunction and mitophagy in Parkinson’s: From familial to sporadic disease. Trends in Biochemical Sciences, 40(4), 200–210. https://doi.org/10.1016/j.tibs.2015.02.003
Pickrell, A. M., & Youle, R. J. (2015). The roles of PINK1, Parkin, and mitochondrial fidelity in Parkinson's disease. Neuron, 85(2), 257–273. https://doi.org/10.1016/j.neuron.2014.12.007
Truban, D., Hou, X., Caulfield, T. R., Fiesel, F. C., & Springer, W. (2017). PINK1, parkin, and mitochondrial quality control: What can we learn about Parkinson’s disease pathobiology? Journal of Parkinson's Disease, 7(1), 13–29. https://doi.org/10.3233/JPD-160871
Blesa, J., Trigo-Damas, I., Quiroga-Varela, A., & Jackson-Lewis, V. R. (2015).
Oxidative stress and Parkinson's disease. Frontiers in Neuroanatomy, 9, 91. https://doi.org/10.3389/fnana.2015.00091
Martin-Maestro, P., Gargini, R., Perry, G., & Avila, J. (2021). Antioxidant therapies in
Parkinson’s disease. Current Neuropharmacology, 19(3), 223–237. https://doi.org/10.2174/1570159X18666201026115018
Mortiboys, H., et al. (2008). Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts. Annals of Neurology, 64(5), 555–565. https://doi.org/10.1002/ana.21524
Yao, L., & Liu, Y. (2022). Precision mitochondrial medicine for Parkinson’s disease: Advances and perspectives. Frontiers in Neuroscience, 16, 841598. https://doi.org/10.3389/fnins.2022.841598