Necroptosis: A Novel Pathway in Neuroinflammation.
Necroptosis: A Novel Pathway in Neuroinflammation.
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坏死性凋亡：神经炎症的新途径
DOI：
10.3389/fphar.2021.701564
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发表时间：
2021
影响因子：
5.6
通讯作者：
Zhuo Y
中科院分区：
文献类型：
--
作者：
Yu Z;Jiang N;Su W;Zhuo Y
神经炎症是神经系统中的一个复杂的炎症过程，预计在神经系统疾病中发挥重要作用。坏死性下垂是由Toll样受体(TLR)-3和TLR-4激动剂、肿瘤坏死因子(TNF)、某些微生物感染和T细胞受体引起的一种坏死，通过破坏死亡细胞和释放细胞内成分来触发天然免疫反应。当caspase-8活性受损时，坏死性下垂信号由受体相互作用蛋白激酶(RIPK)1调节。死亡受体(Death Receptor，DR)激活RIPK1，依赖RIPK1的活性形成一种RIPK1-RIPK3-混合谱系蛋白样蛋白(MLKL)，即复合体II。RIPK3使MLKL磷酸化，最终通过质膜破裂和细胞溶解导致坏死。目前的研究表明，坏死性下垂与阿尔茨海默病、帕金森病和创伤性脑损伤等神经炎症性疾病的发病机制有关。坏死性下垂的抑制剂，如NEC-1(NEC-1)和NEC的稳定变异体(NEC-1s)，已被证明对许多神经系统疾病有效。本文旨在阐明坏死性下垂的发病机制，以及坏死性下垂在神经炎性疾病中的重要作用。总之，这篇文章展示了一种潜在的治疗策略，其中靶向坏死因子可能会改善神经炎性疾病的病理变化和临床症状。
Neuroinflammation is a complex inflammatory process in the nervous system that is expected to play a significant role in neurological diseases. Necroptosis is a kind of necrosis that triggers innate immune responses by rupturing dead cells and releasing intracellular components; it can be caused by Toll-like receptor (TLR)-3 and TLR-4 agonists, tumor necrosis factor (TNF), certain microbial infections, and T cell receptors. Necroptosis signaling is modulated by receptor-interacting protein kinase (RIPK) 1 when the activity of caspase-8 becomes compromised. Activated death receptors (DRs) cause the activation of RIPK1 and the RIPK1 kinase activity-dependent formation of an RIPK1-RIPK3-mixed lineage kinase domain-like protein (MLKL), which is complex II. RIPK3 phosphorylates MLKL, ultimately leading to necrosis through plasma membrane disruption and cell lysis. Current studies suggest that necroptosis is associated with the pathogenesis of neuroinflammatory diseases, such as Alzheimer’s disease, Parkinson’s disease, and traumatic brain injury. Inhibitors of necroptosis, such as necrostatin-1 (Nec-1) and stable variant of Nec (Nec-1s), have been proven to be effective in many neurological diseases. The purpose of this article is to illuminate the mechanism underlying necroptosis and the important role that necroptosis plays in neuroinflammatory diseases. Overall, this article shows a potential therapeutic strategy in which targeting necroptotic factors may improve the pathological changes and clinical symptoms of neuroinflammatory disorders.
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