Parthanatos, A messenger of death

Karen Kate David, Shaida Ahmad Andrabi, Ted M Dawson, Valina Dawson

Research output: Contribution to journalArticle

Abstract

Poly-ADP-ribose polymerase-1 (PARP-1)'s roles in the cell span from maintaining life to inducing death. The processes PARP-1 is involved in include DNA repair, DNA transcription, mitosis, and cell death. Of PARP-1's different cellular functions, its role in cell death is of particular interest to designing therapies for diseases. Genetic deletion of PARP-1 revealed that PARP-1 overactivation underlies cell death in models of stroke, diabetes, inflammation and neurodegeneration. Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into understanding mechanisms downstream of PARP-1 overactivation. Recent evidence shows that poly-ADP ribose (PAR) polymer itself can act as a cell death effector downstream of PARP-1. We coined the term parthanatos after Thanatos, the personification of death in Greek mythology, to refer to PAR-mediated cell death. In this review, we will present evidence and questions raised by these recent findings, and summarize the proposed mechanisms by which PARP-1 overactivation kills. It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 overactivation.

Original languageEnglish (US)
Pages (from-to)1116-1128
Number of pages13
JournalFrontiers in bioscience : a journal and virtual library
Volume14
Issue number3
DOIs
StatePublished - Jan 1 2009

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Keywords

  • Aif
  • Cell death
  • Par polymer
  • Parg
  • Parp-1
  • Parthanatos
  • Review

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

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