Interaction between Poly(ADP-ribose) polymerase-1 and α-synuclein pathology in Parkinson's disease

Poly(ADP-ribose) polymerase-1 (PARP-1) activation and α-synuclein (α-syn) aggregation are neuropathological hallmarks of Parkinson's disease. This review aims to summarize the extensive interplay between these two factors. PARP-1 induces conformational changes in α-syn through structural reorganization mediated by poly(ADP-ribose) (PAR). Stress conditions resulting from PARP-1 overactivation are involved in the post-transcriptional regulation of α-syn. Oxidative and nitrative stress triggered by PARP-1 overactivation participate in the post-translational modifications of α-syn. PAR also contributes to α-syn degradation pathways, thereby influencing α-syn levels. Conversely, α-syn indirectly promotes PARP-1-dependent cell death via reactive oxygen species (ROS), suggesting a possible link through cell death pathways. These findings indicate that intracellular PARP-1, its metabolic products, and α-syn are closely associated, leading to dopaminergic neuronal vulnerability and potentially creating a vicious cycle of toxicity in PD pathology.