| Autor: |
David KK; Institute for Cell Engineering, The Johns Hopkins University School of Medicine, 733 North Broadway St., Suite 711, Baltimore, MD 21205, USA., Andrabi SA, Dawson TM, Dawson VL |
| Jazyk: |
angličtina |
| Zdroj: |
Frontiers in bioscience (Landmark edition) [Front Biosci (Landmark Ed)] 2009 Jan 01; Vol. 14 (3), pp. 1116-28. Date of Electronic Publication: 2009 Jan 01. |
| DOI: |
10.2741/3297 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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