Parthanatos: mitochondrial-linked mechanisms and therapeutic opportunities

被引：445

作者：

Fatokun, Amos A. ^{[1
]}

Dawson, Valina L. ^{[2
,3
,4
,5
,6
]}

Dawson, Ted M. ^{[2
,3
,4
,5
]}

机构：

[1] Univ Nottingham, Sch Biomed Sci, Inst Cell Signalling, Nottingham NG7 2UH, England

[2] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Neuroregenerat Program, Baltimore, MD USA

[3] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stem Cell Program, Baltimore, MD USA

[4] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 2014年 / 171卷 / 08期

关键词：

PARP-1; parthanatos; AIF; mitochondria; cell death; therapy; APOPTOSIS-INDUCING-FACTOR; FOCAL CEREBRAL-ISCHEMIA; POLY(ADP-RIBOSE) POLYMERASE INHIBITION; ADP-RIBOSE POLYMERASE; NITRIC-OXIDE SYNTHASE; NEURONAL CELL-DEATH; IN-VIVO MODELS; SPINAL-CORD; DNA-REPAIR; PHARMACOLOGICAL MANIPULATION;

D O I：

10.1111/bph.12416

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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

引用

页码：2000 / 2016

页数：17

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