School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Int J Mol Sci. 2022 Jun 30;23(13):7292. doi: 10.3390/ijms23137292.
Differential evolution of apoptosis, programmed necrosis, and autophagy, parthanatos is a form of cell death mediated by poly(ADP-ribose) polymerase 1 (PARP1), which is caused by DNA damage. PARP1 hyper-activation stimulates apoptosis-inducing factor (AIF) nucleus translocation, and accelerates nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP) depletion, leading to DNA fragmentation. The mechanisms of parthanatos mainly include DNA damage, PARP1 hyper-activation, PAR accumulation, NAD and ATP depletion, and AIF nucleus translocation. Now, it is reported that parthanatos widely exists in different diseases (tumors, retinal diseases, neurological diseases, diabetes, renal diseases, cardiovascular diseases, ischemia-reperfusion injury...). Excessive or defective parthanatos contributes to pathological cell damage; therefore, parthanatos is critical in the therapy and prevention of many diseases. In this work, the hallmarks and molecular mechanisms of parthanatos and its related disorders are summarized. The questions raised by the recent findings are also presented. Further understanding of parthanatos will provide a new treatment option for associated conditions.
细胞发生程序性坏死和自噬的同时，细胞凋亡也会发生改变，PAR 糖基化（PARthanatos）是一种由聚 ADP 核糖聚合酶 1（PARP1）介导的细胞死亡形式，由 DNA 损伤引起。PARP1 的过度激活会刺激凋亡诱导因子（AIF）核易位，并加速烟酰胺腺嘌呤二核苷酸（NAD）和三磷酸腺苷（ATP）的耗竭，导致 DNA 片段化。PARthanatos 的机制主要包括 DNA 损伤、PARP1 过度激活、PAR 积累、NAD 和 ATP 耗竭以及 AIF 核易位。现在，有报道称 PARthanatos 广泛存在于各种疾病（肿瘤、视网膜疾病、神经退行性疾病、糖尿病、肾脏疾病、心血管疾病、缺血再灌注损伤等）中。PARthanatos 的过度或缺陷会导致病理性细胞损伤；因此，PARthanatos 在许多疾病的治疗和预防中至关重要。在这项工作中，总结了 PARthanatos 的特征和分子机制及其相关疾病。还提出了最近发现提出的问题。进一步了解 PARthanatos 将为相关疾病提供新的治疗选择。
