Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China.
Department of Laboratory Medicine, The Third Xiangya Hospital of Central South University, Changsha, 410013, China.
Cell Mol Life Sci. 2021 Jan;78(1):63-78. doi: 10.1007/s00018-020-03587-8. Epub 2020 Jun 28.
Apoptosis, necrosis and autophagy-dependent cell death are the three major types of cell death. Traditionally, necrosis is thought as a passive and unregulated form of cell death. However, certain necrosis can also occur in a highly regulated manner, referring to regulated necrosis. Depending on the signaling pathways, regulated necrosis can be further classified as necroptosis, pyroptosis, ferroptosis, parthanatos and CypD-mediated necrosis. Numerous studies have reported that regulated necrosis contributes to the progression of multiple injury-relevant diseases. For example, necroptosis contributes to the development of myocardial infarction, atherosclerosis, heart failure and stroke; pyroptosis is involved in the progression of myocardial or cerebral infarction, atherosclerosis and diabetic cardiomyopathy; while ferroptosis, parthanatos and CypD-mediated necrosis participate in the pathological process of myocardial and/or cerebral ischemia/reperfusion injury. Thereby, targeting the pathways of regulated necrosis pharmacologically or genetically could be an efficient strategy for reducing cardio-cerebrovascular injury. Further study needs to focus on the crosstalk and interplay among different types of regulated necrosis. Pharmacological intervention of two or more types of regulated necrosis simultaneously may have advantages in clinic to treat injury-relevant diseases.
细胞凋亡、坏死和自噬依赖性细胞死亡是三种主要的细胞死亡类型。传统上，坏死被认为是一种被动的、不受调节的细胞死亡形式。然而，某些坏死也可以以高度调节的方式发生，称为调节性坏死。根据信号通路的不同，调节性坏死可进一步分为坏死性凋亡、细胞焦亡、铁死亡、PARP 相关坏死和 CypD 介导的坏死。大量研究表明，调节性坏死参与了多种与损伤相关疾病的进展。例如，坏死性凋亡参与了心肌梗死、动脉粥样硬化、心力衰竭和中风的发展；细胞焦亡参与了心肌或脑梗死、动脉粥样硬化和糖尿病心肌病的进展；而铁死亡、PARP 相关坏死和 CypD 介导的坏死参与了心肌和/或脑缺血/再灌注损伤的病理过程。因此，通过药理学或遗传学方法靶向调节性坏死途径可能是减少心脑血管损伤的有效策略。进一步的研究需要集中在不同类型的调节性坏死之间的串扰和相互作用上。同时干预两种或两种以上类型的调节性坏死可能在临床上具有治疗与损伤相关疾病的优势。
