DNA damage induced PARP-1 overactivation confers paclitaxel-induced neuropathic pain by regulating mitochondrial oxidative metabolism.

ABSTRACT:

Aims

Poly (ADP-ribose) polymerase (PARP) has been extensively investigated in human cancers. Recent studies verified that current available PARP inhibitors (Olaparib or Veliparib) provided clinical palliation of clinical patients suffering from paclitaxel-induced neuropathic pain (PINP). However, the underlying mechanism of PARP overactivation in the development of PINP remains to be investigated.

Methods and results

We reported induction of DNA oxidative damage, PARP-1 overactivation, and subsequent nicotinamide adenine dinucleotide (NAD⁺) depletion as crucial events in the pathogenesis of PINP. Therefore, we developed an Olaparib PROTAC to achieve the efficient degradation of PARP. Continuous intrathecal injection of Olaparib PROTAC protected against PINP by inh

SUBMITTER: Ge MM 

PROVIDER: S-EPMC11364515 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature