Lanzhou University Second Hospital, 82 Cuiying Men, Lanzhou 730000, PR China; Orthopedics Key Laboratory of Gansu Province, Lanzhou 730000, PR China.
Lanzhou University Second Hospital, 82 Cuiying Men, Lanzhou 730000, PR China; Orthopedics Key Laboratory of Gansu Province, Lanzhou 730000, PR China.
Int Immunopharmacol. 2024 Sep 10;138:112616. doi: 10.1016/j.intimp.2024.112616. Epub 2024 Jul 2.
Intervertebral disc degeneration (IDD) is the leading cause of low back pain, which is one of the major factors leading to disability and severe economic burden. Necroptosis is an important form of programmed cell death (PCD), a highly regulated caspase-independent type of cell death that is regulated by receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL)-mediated, play a key role in the pathophysiology of various inflammatory, infectious and degenerative diseases. Recent studies have shown that necroptosis plays an important role in the occurrence and development of IDD. In this review, we provide an overview of the initiation and execution of necroptosis and explore in depth its potential mechanisms of action in IDD. The analysis focuses on the connection between NP cell necroptosis and mitochondrial dysfunction-oxidative stress pathway, inflammation, endoplasmic reticulum stress, apoptosis, and autophagy. Finally, we evaluated the possibility of treating IDD by inhibiting necroptosis, and believed that targeting necroptosis may be a new strategy to alleviate the symptoms of IDD.
椎间盘退行性变（IDD）是导致腰痛的主要原因之一，也是导致残疾和严重经济负担的主要因素之一。细胞程序性坏死（Necroptosis）是细胞程序性死亡（PCD）的一种重要形式，是一种高度受调控的、不依赖于半胱天冬酶的细胞死亡形式，受受体相互作用蛋白激酶 1（RIPK1）、RIPK3 和混合谱系激酶结构域样蛋白（MLKL）介导，在各种炎症、感染和退行性疾病的病理生理学中发挥关键作用。最近的研究表明，细胞程序性坏死在 IDD 的发生和发展中起重要作用。在这篇综述中，我们概述了细胞程序性坏死的起始和执行，并深入探讨了其在 IDD 中的潜在作用机制。分析重点关注 NP 细胞程序性坏死与线粒体功能障碍-氧化应激途径、炎症、内质网应激、细胞凋亡和自噬之间的联系。最后，我们评估了通过抑制细胞程序性坏死治疗 IDD 的可能性，并认为针对细胞程序性坏死可能是缓解 IDD 症状的一种新策略。
