'PARP'ing fibrosis: repurposing poly (ADP ribose) polymerase (PARP) inhibitors
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Published on: April 25, 2025
Pooja Dhileepkumar Rao1, Himanshu Sankrityayan1, Anjali Srivastava2
1Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan, 333031, India.
Abstract:
Fibrosis is a wound-healing process that results in tissue scarring and organ dysfunction. Several novel mechanisms of fibrogenesis have been discovered recently. In this review, we focus on the role of poly-ADP ribose polymerase (PARP) in major organ fibrosis, such as lungs, heart, liver, and kidneys. PARP is a dynamic enzyme that modulates different cellular proteins by the addition of PAR groups and mediates an array of cellular events in both normal physiological and pathophysiological states. The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) recently approved several PARP inhibitors, such as olaparib, niraparib, talazoparib, and rucaparib, for the treatment of ovarian and germline BRCA-mutant breast cancers. Consequently, repurposing these drugs could provide an opportunity to counter organ fibrosis.
Insights
Poly(ADP-ribose) polymerase (PARP) plays a key role in organ fibrosis. Existing PARP inhibitors approved for cancer treatment show promise for repurposing to combat fibrotic diseases.
Area of Science:
- Biochemistry
- Cellular Biology
- Pharmacology
Background:
- Fibrosis, characterized by tissue scarring and organ dysfunction, is a pathological outcome of chronic wound healing.
- Recent discoveries have elucidated novel mechanisms driving fibrogenesis across major organs.
- Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in various cellular events, both normal and pathological.
Purpose of the Study:
- To review the role of PARP in the pathogenesis of major organ fibrosis, including the lungs, heart, liver, and kidneys.
- To explore the potential of repurposing FDA- and EMA-approved PARP inhibitors for treating organ fibrosis.
Main Methods:
- Literature review focusing on the function of PARP in fibrogenesis.
- Analysis of existing data on PARP inhibitors used in oncology.
- Discussion of the translational potential for fibrotic diseases.
Main Results:
- PARP modulates cellular proteins and mediates critical cellular events relevant to fibrosis.
- Approved PARP inhibitors (olaparib, niraparib, talazoparib, rucaparib) are effective in treating certain cancers.
- These inhibitors target key pathways implicated in fibrotic processes.
Conclusions:
- PARP is a significant mediator in the development of organ fibrosis.
- Repurposing established PARP inhibitors offers a promising therapeutic strategy to counteract organ fibrosis.
- Further investigation into PARP inhibition for fibrotic conditions is warranted.
