Poly [ADP-ribose] polymerase 1

PARP1 is a poly-ADP-ribose polymerase that catalyzes the addition of ADP-ribose polymers to target proteins, serving as a critical regulator of DNA repair pathways including base excision repair and homologous recombination (UniProt: P09874). The enzyme recognizes DNA breaks, recruits repair factors through serine ADP-ribosylation of histones, and facilitates chromatin decompaction. Beyond DNA repair, PARP1 modulates transcription, regulates the cGAS-STING innate immunity pathway, and influences sleep and neuronal function through its role in sensing DNA damage.

PARP1 is widely expressed across tissues and participates in multiple cellular processes including programmed cell death, replication fork progression, and adipogenesis (UniProt: P09874). The protein can be cleaved by caspases during apoptosis, generating fragments that promote cell death via AIFM1-mediated pathways. No baseline disease associations are documented in UniProt for this protein.

PARP1 is associated with Alzheimer's disease and shows downregulation in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is −1.09 across examined subcellular fractions in TMT-labeled proteomics analysis of human post-mortem AD brain, suggesting reduced PARP1 abundance in the disease state and potential impairment of DNA repair capacity in AD neurons.