Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 171, Issue 8, Pages 2000-2016Publisher
WILEY
DOI: 10.1111/bph.12416
Keywords
PARP-1; parthanatos; AIF; mitochondria; cell death; therapy
Categories
Funding
- University of Nottingham (UK)
- European Commission through its European Union (EU) Seventh Framework (FP7) Marie Curie People Work Programme
- NIH/NINDS [NS067525, NS38377]
- NIDA [DA000266]
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Cells die by a variety of mechanisms. Terminally differentiated cells such as neurones die in a variety of disorders, in part, via parthanatos, a process dependent on the activity of poly (ADP-ribose)-polymerase (PARP). Parthanatos does not require the mediation of caspases for its execution, but is clearly mechanistically dependent on the nuclear translocation of the mitochondrial-associated apoptosis-inducing factor (AIF). The nuclear translocation of this otherwise beneficial mitochondrial protein, occasioned by poly (ADP-ribose) (PAR) produced through PARP overactivation, causes large-scale DNA fragmentation and chromatin condensation, leading to cell death. This review describes the multistep course of parthanatos and its dependence on PAR signalling and nuclear AIF translocation. The review also discusses potential targets in the parthanatos cascade as promising avenues for the development of novel, disease-modifying, therapeutic agents. Linked ArticlesThis article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit
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