Department of Immunology, Key Laboratory of Immunological Environment and Disease, Gusu School, State Key Laboratory of Reproductive Medicine, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Center for Global Health, Nanjing Medical University, Nanjing 211166, China.
Department of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, China.
J Mol Biol. 2022 Feb 28;434(4):167379. doi: 10.1016/j.jmb.2021.167379. Epub 2021 Nov 25.
Pyroptosis is an inflammatory form of cell death executed by transmembrane pore-forming proteins known as gasdermins and can be activated in an inflammasome-dependent or -independent manner. Inflammasome-dependent pyroptosis is triggered in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) and has emerged as an important player in the pathogenesis of multiple inflammatory diseases, mainly by releasing inflammatory contents. More recently, numerous studies have revealed the intricate mechanisms of pyroptosis and its role in the development of neuroinflammation in central nervous system (CNS) diseases. In this review, we summarize current understandings of the molecular and regulatory mechanisms of pyroptosis. In addition, we discuss how pyroptosis can drive different forms of neurological diseases and new promising therapeutic strategies targeting pyroptosis that can be leveraged to treat neuroinflammation.
细胞焦亡是一种由gasdermins 等跨膜孔形成蛋白执行的炎症形式的细胞死亡,可以通过炎症小体依赖或非依赖的方式被激活。炎症小体依赖的细胞焦亡是对病原体相关分子模式(PAMPs)或损伤相关分子模式(DAMPs)的反应而被触发的,并且已经成为多种炎症性疾病发病机制中的一个重要参与者,主要通过释放炎症内容物。最近,许多研究揭示了细胞焦亡的复杂机制及其在中枢神经系统(CNS)疾病神经炎症发展中的作用。在这篇综述中,我们总结了对细胞焦亡的分子和调节机制的现有认识。此外,我们还讨论了细胞焦亡如何驱动不同形式的神经疾病,以及针对细胞焦亡的新的有前途的治疗策略,这些策略可以被用来治疗神经炎症。