Targeting mitochondrial calcium pathways as a potential treatment against Parkinson's disease

Abstract

Parkinson's disease (PD) is a major health problem worldwide affecting millions of people and is a result of neurodegeneration in a small part of the brain known as substantia nigra pars compacta. Aberration in mitochondrial Ca²⁺ homeostasis plays, among several other factors, an important role for the neuronal loss in PD. Mitochondria are vital for cellular physiology, e.g. for ATP generation, and mitochondrial Ca²⁺ is a key player in cell functioning and survival. Mitochondrial Ca²⁺ homeostasis is maintained by a fine balance between the activities of proteins mediating the influx and efflux of Ca²⁺ across mitochondrial membranes. Malfunctioning of these proteins leading to Ca²⁺ overload promotes ROS generation, which induces cell death by triggering the opening of mitochondrial permeability transition pore. Till now PD remains incurable and the "gold standard" drug which can only delays the disease progression is l-Dopa from the 1960s and therefore, the situation warrants the search for novel targets for the treatment of the PD patients. In this review, we summarize the current views that suggest mitochondrial Ca²⁺ regulatory pathways are good candidates for the treatment of PD.

Keywords: Ca(2+); MCU; Mitochondria; NCLX; Parkinson’s disease; VDAC.