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PARP-1: a critical regulator in radioprotection and radiotherapy-mechanisms, challenges, and therapeutic

Wen-Hao Li1, Fei Wang1, Gui-Yuan Song2

  • 1School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, China.

Frontiers in Pharmacology
|June 23, 2023
PubMed

Insights

Poly (ADP-ribose) polymerase 1 (PARP-1) is crucial for DNA repair and radiation response. PARP inhibitors show promise for improving outcomes in radiation damage, despite challenges.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Oncology

Background:

  • Poly (ADP-ribose) polymerase 1 (PARP-1) is a key enzyme in DNA repair pathways.
  • PARP inhibitors are emerging as effective cancer therapeutics.
  • Understanding PARP-1's role is vital for advancing disease treatment.

Purpose of the Study:

  • To review the current literature on PARP-1 mechanisms in radioprotection and radiotherapy.
  • To explore the multifaceted roles of PARP-1 in cellular responses to radiation.
  • To assess the therapeutic potential of PARP-1 inhibitors in radiation-related conditions.

Main Methods:

  • Literature search of the PubMed database.
  • Summarization of studies on PARP inhibitors and their interactions.
  • Analysis of PARP-1's relationship with DNA, p53/ROS, NF-κB/DNA-PK, and caspase3/AIF.

Main Results:

  • PARP-1 is essential for repairing radiation-induced DNA damage, including single-, intra-, and inter-strand breaks.
  • PARP-1 activity significantly increases upon DNA binding and regulates radiation response.
  • PARP-1 influences gene expression by modulating transcription factors like NF-κB and p53, and molecules such as ROS, Caspase 3, and AIF.

Conclusions:

  • PARP-1 plays a significant role in both physiological and pathological processes, particularly concerning ionizing radiation.
  • PARP-1 inhibitors demonstrate potential in mitigating ionizing radiation damage.
  • Further development of PARP-1 inhibitors is needed to enhance clinical outcomes for radiation-exposed patients.
Keywords:
Caspese-3/AIFNF-κB/DNA-PKPARP inhibitorionizing radiationp53/ROS

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