多发性硬化症（MS）是一种以脱髓鞘为特征的中枢神经系统（CNS）慢性炎症性疾病。目前多发性硬化症的治疗方案主要集中在免疫抑制上，但其疗效可能有限。最近的研究表明神经损伤诱导蛋白 1 (NINJ1) 在 MS 发病机制中具有潜在作用。 NINJ1 是一种参与细胞死亡和炎症的蛋白质，可能通过增强血脑屏障穿越来促进中枢神经系统炎症细胞的浸润和激活；在细胞死亡过程中增强质膜破裂，导致炎症介质的释放和进一步的组织损伤。本综述探讨了 NINJ1 参与 MS 的新证据。它讨论了 NINJ1 如何介导免疫细胞穿过血脑屏障的迁移、加剧神经炎症并参与质膜破裂相关的损伤。最后，该综述探讨了针对 NINJ1 的潜在治疗策略，以改善 MS 管理。缩写：MS，多发性硬化症； CNS，中枢神经系统； BBB，血脑屏障； GSDMD、Gasdermin-D； EAE，实验性自身免疫性脑炎； HMGB-1，高迁移率族box-1蛋白； LDH，乳酸脱氢酶； PMR，质膜破裂； DMF、富马酸二甲酯； DUSP1，双特异性磷酸酶1； PAMP，病原体相关分子模式； DAMP，危险相关分子模式； PRR，模式识别受体； GM-CSF、粒细胞-巨噬细胞集落刺激因子； IFN-γ、干扰素γ； TNF，肿瘤坏死因子； APC，抗原呈递细胞； EC，内皮细胞； TGF-β、转化生长因子-β； PBMC，外周血单个核细胞； FACS，荧光激活细胞分选； MCP-1，单核细胞趋化蛋白-1； NLRP3，含Pyrin结构域3； TCR，T细胞受体； ROS，活性氧； AP-1，激活蛋白-1； ANG1，血管生成素1； BMDM，骨髓源性巨噬细胞； Arp2/3，肌动蛋白相关蛋白2/3； EMT，上皮间质转化； FAK，粘着斑激酶； LIMK1，LIM 结构域激酶 1； PAK1、p21 激活激酶 1； Rac1，Ras相关C3肉毒毒素底物1； β-cat，β-caten； MyD88，骨髓分化初级反应基因88； TIRAP，含有 Toll/interleukin-1 受体结构域的衔接蛋白； TLR4，Toll 样受体 4； IRAKs，白介素-1 受体相关激酶； TRAF6，TNF受体相关因子6； TAB2/3、TAK1结合蛋白2/3； TAK1，转化生长因子-β-激活激酶1； JNK，c-Jun N 末端激酶； ERK1/2，细胞外信号调节激酶 1/2； IKK，κ B 激酶抑制剂； IκB，NF-κB 抑制剂； NF-κB，核因子κ-B； AP-1，激活蛋白-1； ASC，含有 CARD 的凋亡相关斑点样蛋白； NEK7，NIMA 相关激酶 7； NLRP3，含Pyrin结构域3； CREB，cAMP 反应元件结合蛋白。版权所有 © 2024。由 Elsevier B.V. 出版。

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination. Current treatment options for MS focus on immunosuppression, but their efficacy can be limited. Recent studies suggest a potential role for nerve injury-induced protein 1 (NINJ1) in MS pathogenesis. NINJ1, a protein involved in cell death and inflammation, may contribute to the infiltration and activation of inflammatory cells in the CNS, potentially through enhanced blood-brain barrier crossing; enhancing plasma membrane rupture during cell death, leading to the release of inflammatory mediators and further tissue damage. This review explores the emerging evidence for NINJ1's involvement in MS. It discusses how NINJ1 might mediate the migration of immune cells across the blood-brain barrier, exacerbate neuroinflammation, and participate in plasma membrane rupture-related damage. Finally, the review examines potential therapeutic strategies targeting NINJ1 for improved MS management. Abbreviations: MS, Multiple sclerosis; CNS, Central nervous system; BBB, Blood-brain barrier; GSDMD, Gasdermin-D; EAE, Experimental autoimmune encephalitis; HMGB-1, High mobility group box-1 protein; LDH, Lactate dehydrogenase; PMR, Plasma membrane rupture; DMF, Dimethyl fumarate; DUSP1, Dual-specificity phosphatase 1; PAMPs, Pathogen-associated molecular patterns; DAMPs, Danger-associated molecular patterns; PRRs, Pattern recognition receptors; GM-CSF, Granulocyte-macrophage colony stimulating factor; IFN-γ, Interferon gamma; TNF, Tumor necrosis factor; APCs, Antigen-presenting cells; ECs, Endothelial cells; TGF-β, Transforming growth factor-β; PBMCs, Peripheral blood mononuclear cells; FACS, Fluorescence-activated cell sorting; MCP-1, Monocyte chemoattractant protein-1; NLRP3, Pyrin domain-containing 3; TCR, T cell receptor; ROS, Reactive oxygen species; AP-1, Activator protein-1; ANG1, Angiopoietin 1; BMDMs, Bone marrow-derived macrophages; Arp2/3, actin-related protein 2/3; EMT, epithelial-mesenchymal transition; FAK, focal adhesion kinase; LIMK1, LIM domain kinase 1; PAK1, p21-activated kinases 1; Rac1, Ras-related C3 botulinum toxin substrate 1; β-cat, β-caten; MyD88, myeloid differentiation primary response gene 88; TIRAP, Toll/interleukin-1 receptor domain-containing adapter protein; TLR4, Toll-like receptor 4; IRAKs, interleukin-1 receptor-associated kinases; TRAF6, TNF receptor associated factor 6; TAB2/3, TAK1 binding protein 2/3; TAK1, transforming growth factor-β-activated kinase 1; JNK, c-Jun N-terminal kinase; ERK1/2, Extracellular Signal Regulated Kinase 1/2; IKK, inhibitor of kappa B kinase; IκB, inhibitor of NF-κB; NF-κB, nuclear factor kappa-B; AP-1, activator protein-1; ASC, Apoptosis-associated Speck-like protein containing a CARD; NEK7, NIMA-related kinase 7; NLRP3, Pyrin domain-containing 3; CREB, cAMP response element-binding protein.Copyright © 2024. Published by Elsevier B.V.