PARkinson's: From cellular mechanisms to potential therapeutics.

ABSTRACT

Our understanding of the progression and mechanisms underlying the onset of Parkinson's disease (PD) has grown enormously in the past few decades. There is growing evidence suggesting that poly (ADP-ribose) polymerase 1 (PARP-1) hyperactivation is involved in various neurodegenerative disorders, including PD, and that poly (ADP-ribose) (PAR)-dependent cell death is responsible for neuronal loss. In this review, we discuss the contribution of PARP-1 and PAR in the pathological process of PD. We describe the potential pathways regulated by the enzyme, review clinically relevant PARP-1 inhibitors as potential disease-modifying therapeutics for PD, and outline important factors that need to be considered for repurposing PARP-1 inhibitors for use in PD.