IMR Press / FBL / Volume 14 / Issue 3 / DOI: 10.2741/3297

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Parthanatos, a messenger of death

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1 Institute for Cell Engineering, The Johns Hopkins University School of Medicine, 733 North Broadway St., Suite 711, Baltimore, MD 21205, USA
2 Cellular and Molecular Medicine Program, The Johns Hopkins University School of Medicine, 733 North Broadway St., Suite 711, Baltimore, MD 21205, USA
3 Departments of Neurology, The Johns Hopkins University School of Medicine, 733 North Broadway St., Suite 711, Baltimore, MD 21205, USA
4 Neuroscience Physiology, The Johns Hopkins University School of Medicine, 733 North Broadway St., Suite 711, Baltimore, MD 21205, USA
Academic Editor:Pal Pacher
Front. Biosci. (Landmark Ed) 2009, 14(3), 1116–1128; https://doi.org/10.2741/3297
Published: 1 January 2009
(This article belongs to the Special Issue Nitric oxide, superoxide and peroxynitrite in cardiovascular diseases)
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.

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