Emerging role of PARP-1 and PARthanatos in ischemic stroke.

Emerging role of PARP-1 and PARthanatos in ischemic stroke.
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DOI:
10.1111/jnc.15464
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发表时间:
2022-01
影响因子:
4.7
通讯作者:
Wang Y
Wang Y
中科院分区:
医学2区
文献类型:
--
作者:
Liu S;Luo W;Wang Y

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细胞死亡是神经系统疾病的一个关键特征,包括中风和神经退行性疾病。对多种缺血/缺氧小鼠模型的研究表明,聚(ADP-核糖)聚合酶 1 (PARP-1) 依赖性细胞死亡(也称为 PARthanatos)在缺血性神经元细胞死亡和疾病进展中发挥着关键作用。 PARthanatos 拥有独特的触发器、处理器和执行器,可传达高度精心策划和编程的信号级联。除了通过其各种靶标的 PARylation 在基因转录、DNA 损伤修复和能量稳态中发挥作用之外,神经元和神经胶质细胞中的 PARP-1 激活还导致缺血/再灌注后的脑损伤。 PARP-1的药理抑制或基因缺失可减少梗塞体积、消除炎症并改善中风神经功能的恢复。在这里,我们回顾了 PARP-1 和 PARthanatos 在中风中的作用及其治疗潜力。
Cell death is a key feature of neurological diseases, including stroke and neurodegenerative disorders. Studies in a variety of ischemic/hypoxic mouse models demonstrate that poly(ADP-ribose) polymerase 1 (PARP-1)-dependent cell death, also named PARthanatos, plays a pivotal role in ischemic neuronal cell death and disease progress. PARthanatos has its unique triggers, processors, and executors that convey a highly orchestrated and programmed signaling cascade. In addition to its role in gene transcription, DNA damage repair, and energy homeostasis through PARylation of its various targets, PARP-1 activation in neuron and glia attributes to brain damage following ischemia/reperfusion. Pharmacological inhibition or genetic deletion of PARP-1 reduces infarct volume, eliminates inflammation, and improves recovery of neurological functions in stroke. Here, we reviewed the role of PARP-1 and PARthanatos in stroke and their therapeutic potential.
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