Open Access
Parthanatos, a messenger of death
Karen Kate David1,Shaida Ahmad Andrabi1,Ted Murray Dawson1,Valina Lynn Dawson1
Institute for Cell Engineering, The Johns Hopkins University School of Medicine, 733 North Broadway St., Suite 711, Baltimore, MD 21205, USA
DOI: 10.2741/3297 Volume 14 Issue 3, pp.1116-1128
Published: 01 January 2009
(This article belongs to the Special Issue Nitric oxide, superoxide and peroxynitrite in cardiovascular diseases)

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.

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Karen Kate David, Shaida Ahmad Andrabi, Ted Murray Dawson, Valina Lynn Dawson. Parthanatos, a messenger of death. Frontiers in Bioscience-Landmark. 2009. 14(3); 1116-1128.