Recovery of Impaired Mitochondrial Dynamics and Quality Control Mechanisms in Parkinson's Disease

Parkinson’s Disease (PD) is a progressive neurological disorder characterized by tremors, rigidity, and slowness of movements. Most often observed in those aged 60 and above, the perniciousness of this disease lies not just in its global reach, affecting many people worldwide, but also in how no current effective disease-modifying therapy has yet to been established. While the pathophysiology of PD is multifactorial, mitochondrial dysfunction plays an established central role. Through efforts directed towards understanding mitochondrial dysfunction as a precipitating factor of parkinsonism, it has yielded valued insights into the mechanisms governing this disease. Nevertheless, the established importance of maintaining mitochondrial health through mitochondrial dynamics and quality control mechanisms in neuronal survival, and its pervasive dysregulation in PD, represents a key therapeutic target for future therapies. This review will serve to elucidate the pertinence of mitochondrial dysfunction as a therapeutic target in PD and discuss evolving approaches taken to address the recovery of such impairments.

Abbreviations: PD - Parkinson’s Disease; Mito-QC - Mitochondrial Quality Control; ROS - Reactive Oxygen Species; Drp1 - Dynamin-related protein 1; OMM - Outer Mitochondrial Membrane; ALP – Autophagy Lysosomal Pathway; iPSCs - Induced Pluripotent Stem Cells; PMD - Peptide Mediated Allogeneic Delivery; bNIRS - Broadband Near-Infrared Spectroscopy

Keywords: Mitochondrial dysfunction; Mitochondrial Quality Control Mechanism; Alpha-synuclein; PINK1/Parkin activity; Drp1 proteins; Miro 1/2 proteins

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