Poly(ADP-ribose) polymerase and cellular thiol-dependent redox systems (PARP/Thiol-Redox)

Poly(ADP-ribose) polymerase (PARP) and cellular thiol-dependent redox systems, including the glutathione and thioredoxin pathways, constitute a critical axis in the maintenance of genomic integrity and redox homeostasis. PARP1, the most prominent member of the PARP family, functions as a molecular sensor of DNA damage, facilitating the repair of single-strand breaks via the base excision repair pathway (UniProt P09874). Thiol-dependent systems are the primary cellular defense against oxidative stress, utilizing reducing equivalents to neutralize reactive oxygen species and maintain protein function (PubMed PMID: 28235563). The synergy between these systems is therapeutically significant; PARP inhibition leads to the accumulation of DNA damage, while the depletion of thiol-dependent antioxidants increases the burden of oxidative lesions. This dual-targeting approach is particularly effective in oncology, where it can induce synthetic lethality in homologous recombination-deficient cells or trigger parthanatos, a form of programmed cell death driven by PARP overactivation and NAD+ depletion (PubMed PMID: 15548208). Clinical applications primarily focus on PARP inhibitors like olaparib and niraparib, often in the context of BRCA-mutated cancers, with emerging research exploring the modulation of redox systems to enhance therapeutic efficacy (PubChem CID 23667635).

Other names

PARPPoly(ADP-ribose) polymeraseGlutathione systemThioredoxin systemGSH/Trx systemsPARP-1

Inhibition of PARP-mediated DNA repair and disruption of thiol-dependent antioxidant defenses to induce genomic instability and oxidative stress-induced cell death.