Targeting Mitochondria as a Therapeutic Approach for Parkinson's Disease

Abstract

Neurodegeneration is among the most critical challenges that involve modern societies and annually influences millions of patients worldwide. While the pathophysiology of Parkinson's disease (PD) is complicated, the role of mitochondrial is demonstrated. The in vitro and in vivo models and genome-wide association studies in human cases proved that specific genes, including PINK1, Parkin, DJ-1, SNCA, and LRRK2, linked mitochondrial dysfunction with PD. Also, mitochondrial DNA (mtDNA) plays an essential role in the pathophysiology of PD. Targeting mitochondria as a therapeutic approach to inhibit or slow down PD formation and progression seems to be an exciting issue. The current review summarized known mutations associated with both mitochondrial dysfunction and PD. The significance of mtDNA in Parkinson's disease pathogenesis and potential PD therapeutic approaches targeting mitochondrial dysfunction was then discussed.

Keywords: Mitochondrial dysfunction; Neurodegeneration; Parkinson’s disease.

Fig. 1

Schematic presentation of interaction between mitochondrial dysfunction and Parkinson's disease and therapeutic approaches that target mitochondria to treat PD. Intracellular accumulation of α-synuclein, respiratory chain dysfunction, failure in the mechanisms involved in mitophagy processes, and alterations in mtDNA such as depletion, mutation, and deletion are prominent causative factors that link mitochondrial dysfunction to PD. Targeting mitochondria using mitochondrial enhancers, mitophagy enhancers, exercise, and mitochondrial transplantations are among the most important therapeutic approaches that could efficiently implicated for PD treatment