氧化磷脂酰胆碱沉积通过IL-1β信号驱动进行性多发性硬化症小鼠模型的慢性神经变性，这一成果由萨斯喀彻温大学Yifei Dong课题组经过不懈努力而取得。该研究于2025年12月1日发表于国际一流学术期刊《自然—神经科学》杂志上。

本研究表明，小鼠中枢神经系统中立体定向OxPC沉积可诱导慢性区室化病变，其病理特征与P-MS中发现的慢性活动性病变相似。使用该模型，研究小组发现尽管小胶质细胞保护CNS免受慢性神经变性，但在慢性OxPC病变中，它们也被单核细胞来源的巨噬细胞所取代。衰老是P-MS的一个危险因素，改变了慢性OxPC病变的小胶质细胞组成并加剧了神经退行性变。Casp1/ casp4缺陷小鼠的疾病病理改善和IL-1R1的阻断表明，IL-1β信号通路有助于慢性OxPC积累和神经变性。这些结果强调了OxPCs和IL-1β是MS慢性神经退行性变的潜在驱动因素，并表明它们的中和可以有效治疗P-MS。

研究人员表示，氧化磷脂酰胆碱（OxPCs）是进行性多发性硬化症（P-MS）期间中枢神经系统（CNS）氧化应激升高的神经毒性副产物。OxPCs如何参与P-MS的病理生理机制尚不清楚。

附：英文原文

Title: Oxidized phosphatidylcholines deposition drives chronic neurodegeneration in a mouse model of progressive multiple sclerosis via IL-1β signaling

Author: Yu, Ruoqi, Lozinski, Brian M., Seifert, Ally, Ta, Khanh, Zandee, Stephanie, Kaushik, Deepak K., Park, Jian, Klement, Wendy, Larouche, Sandra, Tsimikas, Sotirios, Witztum, Joseph L., McGavern, Dorian B., Prat, Alexandre, Dong, Yifei

Issue&Volume: 2025-12-01

Abstract: Oxidized phosphatidylcholines (OxPCs) are neurotoxic byproducts of oxidative stress elevated in the central nervous system (CNS) during progressive multiple sclerosis (P-MS). How OxPCs contribute to the pathophysiology of P-MS is unclear. Here we show that stereotactic OxPC deposition in the CNS of mice induces a chronic compartmentalized lesion with pathological features similar to chronic active lesions found in P-MS. Using this model, we found that although microglia protected the CNS from chronic neurodegeneration, they were also replaced by monocyte-derived macrophages in chronic OxPC lesions. Aging, a risk factor for P-MS, altered microglial composition and exacerbated neurodegeneration in chronic OxPC lesions. Amelioration of disease pathology in Casp1/Casp4-deficient mice and by blockade of IL-1R1 indicate that IL-1β signaling contributes to chronic OxPC accumulation and neurodegeneration. These results highlight OxPCs and IL-1β as potential drivers of chronic neurodegeneration in MS and suggest that their neutralization could be effective for treating P-MS.

DOI: 10.1038/s41593-025-02113-y

Source: https://www.nature.com/articles/s41593-025-02113-y