Parthanatos, a messenger of death.
Parthanatos, a messenger of death.
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DOI：
10.2741/3297
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Dawson VL
中科院分区：
文献类型：
--
作者：
David KK;Andrabi SA;Dawson TM;Dawson VL
聚ADP核糖聚合酶-1（PARP-1）在细胞中的多重作用包括维持生命和诱导死亡。PARP-1参与的过程包括但不限于DNA修复、DNA转录、有丝分裂和细胞死亡。在PARP-1的不同细胞功能中，其在细胞死亡中的积极作用对于设计疾病疗法特别感兴趣。PARP-1的基因缺失揭示了PARP-1的过度激活是中风、糖尿病、炎症和神经变性实验模型中细胞死亡的基础。由于干扰PARP-1介导的细胞死亡将在临床上是有益的，因此已经投入了大量的努力来设计PARP-1抑制剂和理解PARP-1过度活化的下游机制。PARP-1过度激活可能通过烟酰胺腺嘌呤二核苷酸（NAD+）消耗消耗细胞能量和释放细胞死亡效应物凋亡诱导因子（AIF）来杀死细胞。出乎意料的是，最近的证据表明，聚ADP核糖（PAR）聚合物本身，而不是NAD+的消耗是细胞毒性的来源。因此，PAR聚合物充当PARP-1介导的细胞死亡信号传导下游的细胞死亡效应物。我们在Thanatos之后创造了parthanatos这个词，Thanatos是希腊神话中死亡的化身，指PAR介导的细胞死亡。在这篇综述中，我们将总结PARP-1过度激活杀死的拟议机制。我们将为parthanatos提供证据，以及这些最新发现所提出的问题。很明显，对parthanatos的进一步了解为改善与PARP-1过度激活相关的疾病的治疗开辟了新的途径。
Poly-ADP-ribose polymerase-1 (PARP-1)'s multiple roles in the cell span from maintaining life to inducing death. The processes PARP-1 is involved in include, but are not limited to DNA repair, DNA transcription, mitosis, and cell death. Of PARP-1's different cellular functions, its active role in cell death is of particular interest to designing therapies for diseases. Genetic deletion of PARP-1 revealed that PARP-1 over activation underlies cell death in experimental 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 designing PARP-1 inhibitors and understanding mechanisms downstream of PARP-1 over activation. PARP-1 overactivation may kill by depleting cellular energy through nicotinamide adenine dinucleotide (NAD+) consumption, and by releasing the cell death effector apoptosis-inducing factor (AIF). Unexpectedly, recent evidence shows that poly-ADP ribose (PAR) polymer itself, and not the consumption of NAD+ is the source of cytotoxicity. Thus, PAR polymer acts as a cell death effector downstream of PARP-1-mediated cell death signaling. 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 summarize the proposed mechanisms by which PARP-1 overactivation kills. We will present evidence for parthanatos, and the questions raised by these recent findings. It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 over activation.
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影响因子：
11.4
作者：
Cheung, Eric C. C.;Joza, Nicholas;Slack, Ruth S.
通讯作者：
Slack, Ruth S.
DOI：
10.1073/pnas.0606526103
发表时间：
2006-11-28
影响因子：
11.1
作者：
Andrabi, Shaida A.;Kim, No Soo;Dawson, Ted M.
通讯作者：
Dawson, Ted M.
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
3.9
作者：
BECKMAN, JS;CROW, JP
通讯作者：
CROW, JP
影响因子：
5.3
作者：
Cheung, ECC;Melanson-Drapeau, L;Slack, RS
通讯作者：
Slack, RS