DJ-1/PARK7: A new therapeutic target for neurodegenerative disorders

Abstract

DJ-1, encoded in a causative gene of familial Parkinson's disease (PARK7), has multiple functions: it works as an antioxidant, in transcriptional regulation, as a molecular chaperone and in protein degradation. Three types of pathogenic mutants of DJ-1 (M26I, D149A and L166P) have been reported to disrupt proper structures and lead to a loss of function. DJ-1 receives oxidation at the cysteine residue, and the degree of oxidation at the C106 residue determines DJ-1 activity. In this decade, DJ-1 has been reported to suppress the progression of various neurodegenerative disorders in animal models. The administration of recombinant wild-type DJ-1 protein suppresses the neuronal loss associated with both Parkinson's disease and ischemic stroke in rats. Furthermore, in studies focused on DJ-1 as the therapeutic target, compounds that have the capacity of binding to DJ-1 at the C106 residue have been reported to exert therapeutic effects on various neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and ischemic stroke. DJ-1 and DJ-1-targeting molecules/compounds will be useful therapeutic targets for various neurodegenerative disorders due to their various functions such as antioxidant capacity, chaperone function and as a proteolytic pathway.