Mitophagy in Parkinson's disease: From pathogenesis to treatment target

Abstract

Healthy mitochondria play an essential role in energy metabolism, but dysfunctional mitochondria can cause perturbations in cellular processes which can ultimately lead to cell death. The process which selectively removes and degrades dysfunctional mitochondria, mitophagy, protects against the accumulation of abnormal mitochondria and hence has a protective role in maintaining cell health. Increasing numbers of studies have linked defective mitophagy to a range of diseases, including Parkinson's disease (PD). Whilst current treatment strategies in PD can improve the classical motor symptoms of the disease, they are also associated with often severe side-effects, and generally do not tackle the underlying progressive neurodegeneration seen in the disease. The identification of novel treatment targets, such as mitophagy, are therefore of increasing interest in PD research. This review will begin by outlining the process of mitophagy, before examining evidence implicating mitophagy in both monogenic and sporadic forms of PD, drawing links between mitophagy and wider pathological processes such as protein accumulation and neuroinflammation. Finally, this review will examine the diverse strategies employed to promote mitophagy so far, discuss considerations arising from these studies, and present a framework for eventual assessment of mitophagy-promoting compounds and their viability as a treatment strategy for PD patients.

Keywords: Mitochondria; Mitophagy; Neurodegeneration; Parkinson's disease; Therapeutics.