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Poly(ADP-ribose) polymerase-1 and its ambiguous role in cellular life and death

Maria Castedo1,2, Antoine Lafarge1,2,3, Guido Kroemer1,2,4

  • 1Equipe 11 labellisée par la Ligue contre le Cancer, Université de Paris Cité, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, 75006 Paris, France.

Cell Stress
|February 6, 2023
PubMed

Insights

Poly(ADP-ribose) polymerase-1 (PARP1) inhibition shows protective effects against neurological diseases but aids cancer cell death. PARP1

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Neuroscience

Background:

  • Poly(ADP-ribose) polymerase-1 (PARP1) is implicated in DNA repair and cell death pathways.
  • PARP1 activity has been linked to neuroprotection in models of cerebral ischemia and Parkinson's disease.
  • PARP1 inhibitors are utilized in cancer therapy to induce cell death.

Purpose of the Study:

  • To elucidate the context-dependent role of PARP1 in cell fate.
  • To investigate the dual role of PARP1 in neurological protection and cancer therapy.
  • To explore the ambiguous involvement of PARP1 in organismal aging.

Main Methods:

  • Gene deletion studies in mice.
  • Pharmacological inhibition of PARP1.
  • Analysis of cell death pathways, including parthanatos.
  • Assessment of DNA damage response in cancer cells.

Main Results:

  • PARP1 deletion or inhibition protects against cerebral ischemia and Parkinson's disease in mice.
  • PARP1 inhibition in cancer cells leads to amplified DNA damage and cell death.
  • Excessive PARP1 activation is associated with parthanatos, a specific cell death pathway.

Conclusions:

  • PARP1 plays a critical, context-dependent role in determining cell fate.
  • PARP1 inhibition offers therapeutic potential in both neurological disorders and cancer, albeit through different mechanisms.
  • The role of PARP1 in aging requires further investigation due to its ambiguous nature.
Keywords:
DNA damagePARP1 inhibitionagingcancercellular stress responseneurological diseasesparthanatos

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