Caspase-Poly (ADP-ribose) polymerase pathway (Caspase-PARP pathway) (Caspase-PARP pathway)

The Caspase-PARP pathway is a fundamental biochemical cascade that regulates the transition between DNA repair and programmed cell death (apoptosis). Central to this pathway is the proteolytic cleavage of Poly (ADP-ribose) polymerase (PARP), primarily PARP-1, by executioner caspases such as Caspase-3 and Caspase-7 (Lazebnik et al., 1994, Nature). Under normal conditions, PARP-1 detects DNA strand breaks and facilitates repair; however, during apoptosis, its cleavage by caspases inactivates the enzyme, preventing the depletion of cellular ATP and ensuring the orderly completion of cell death (D'Amours et al., 1999, Biochem. J.). In oncology, this pathway is exploited through PARP inhibitors like Olaparib and Niraparib, which induce synthetic lethality in tumors with BRCA1/2 mutations by trapping PARP on DNA and preventing alternative repair mechanisms (Lord & Ashworth, 2017, Science). Conversely, caspase inhibitors like Emricasan have been investigated to mitigate excessive cell death in conditions such as liver cirrhosis and neurodegeneration (Shiffman et al., 2019, J. Hepatol.). Monitoring the levels of cleaved PARP (cPARP) serves as a critical biomarker for assessing the efficacy of pro-apoptotic therapies in clinical settings.

Other names

Caspase-PARP axisCaspase-mediated PARP cleavageApoptotic signaling pathway

PARP inhibitors (e.g., Olaparib) inhibit DNA repair and trap PARP on DNA, leading to double-strand breaks and synthetic lethality in BRCA-deficient cells (Lord & Ashworth, 2017, Science). Caspase inhibitors (e.g., Emricasan) bind to the active site of caspases to prevent the cleavage of downstream substrates like PARP, thereby inhibiting apoptosis (Shiffman et al., 2019, J. Hepatol.).