NINJ1: A new player in multiple sclerosis pathogenesis and potential therapeutic target

作者：Yinbin Xu, Enhao Zhang, Liangzhe Wei, Zifeng Dai, Siqi Chen, Shengjun Zhou, Yi Huang · 发表于：International Immunopharmacology · 年份：2024 · DOI：10.1016/j.intimp.2024.113021 · 被引用次数：12 · 研究领域：Multiple Sclerosis Research Studies、Inflammasome and immune disorders、Immune Response and Inflammation

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-macroph...