Poly(ADP-ribose) polymerase 1 (PARP1) – Caspase pathway (PARP1–Caspase pathway)

The caspase–poly(ADP-ribose) polymerase pathway is a central axis in the regulation of programmed cell death (apoptosis). PARP1 is a nuclear enzyme involved in DNA repair; during apoptosis, it is cleaved by executioner caspases (mainly caspase-3 and caspase-7) into an N-terminal (24 kDa) and C-terminal (85–89 kDa) fragment, which inactivates PARP1’s DNA repair activity. This cleavage controls cellular energy consumption, prevents inefficient DNA repair in dying cells, and is a hallmark of apoptosis. Overactivation of PARP1 in response to extensive DNA damage can also lead to cell death via ATP and NAD+ depletion, while regulated cleavage by caspases ensures orderly cell death rather than necrosis. Both PARP1 and caspases are drug targets: PARP inhibitors are FDA-approved for some cancers; caspase inhibitors are experimental and mostly research tools. The pathway is implicated in cancer, neurodegeneration, ischemic injuries, and immune/inflammatory responses.

Other names

Caspase-PARP pathwayCaspase-mediated PARP cleavage pathwayPARP-caspase axis

PARP inhibitors block DNA repair, increasing cell death in DNA-damaged cells (notably in cancer therapy). Caspase inhibitors prevent apoptosis and PARP1 cleavage by inhibiting caspase activity.