Chemical Strategies for Activating PINK1, a Protein Kinase Mutated in Parkinson's Disease

Abstract

PINK1 is a ubiquitously expressed mitochondrial serine/threonine protein kinase that has emerged as a key player in mitochondrial quality control. This protein kinase came to prominence in the mid-2000s, when PINK1 mutations were found to cause early onset Parkinson's disease (PD). As most of the PD-related mutations occurred in the kinase domain and impaired PINK1's catalytic activity, it was suggested that small molecules that activated PINK1 would maintain mitochondrial quality control and, as a result, have neuroprotective effects. Working on this hypothesis, a few small-molecule PINK1 activators that offer critical insights and distinct approaches for activating PINK1 have been discovered. Herein, we briefly highlight the discovery of these small molecules and offer insight into the future development of small-molecule PINK1 activators as potential treatments for PD.

Keywords: PINK1; Parkinson's disease; activation; kinases.