Emerging concepts of mitochondrial dysfunction in Parkinson's disease progression: Pathogenic and therapeutic implications

Abstract

Mitochondria are very dynamic organelle which plays a multifactorial role for a broad range of physiological processes inside the cell to maintain neural circuit integrity. They are required for the generation of cellular energy, regulation of calcium homeostasis and controlling programmed cell death. Defective mitochondrial homeostasis is frequently reported in a broad range of neurological disorders. Many lines of evidence suggest that it plays an essential role in aging and neurodegeneration. Parkinson's disease (PD), the second most prevalent neurodegenerative disorder and its aetiology is still largely unexplored. Overwhelming evidences indicate that mitochondrial dysfunction plays a central role in PD pathogenesis. Various genes involved in maintaining the mitochondrial homeostasis are also associated with the PD pathophysiology. Alterations in mitochondrial functions such as generation of reactive oxygen species (ROS), impaired mitophagy, altered mitochondrial dynamics, impaired mitochondrial biogenesis and Ca²⁺ buffering may precede the development of PD pathology. In addition, recent studies have also shown the involvement of gut microbiota in the pathogenesis of several neurodegenerative diseases including PD. In this context, mitochondria-targeted therapies that can ameliorate the mitochondrial abnormalities may have great promise in the prevention and treatment of PD. This review aims to discuss the mitochondrial dysfunction associated with PD pathogenesis, influence of microbiome on mitochondrial regulation and various mitochondrial targeted therapies that can improve the mitochondrial function and deplete the severity of the disease.

Keywords: Mitochondrial quality control; Parkinson’s disease; Substantia nigra pars compacta; Therapeutics.