医学创新论坛第42期
CIMR Wednesday Lecture Series
时间:2024年10月9日(周三)下午4:00
地点:首都医科大学基础科研楼北楼一层逸夫报告厅
主持人:柴国梁
首都医学科学创新中心研究员
报告人:王鑫
厦门大学神经科学研究所教授
报告题目:
阿尔茨海默病的神经免疫机制
摘要:
β2-microglobulin (B2M), a critical component of MHC-I and an amyloid itself, emerges as a key player in Alzheimer's disease (AD). Our research reveals B2M co-aggregates with β-amyloid (Aβ), exacerbating pathology. Inhibiting B2M-Aβ co-aggregation significantly reduces amyloid pathology and cognitive deficits in AD models. Crucially, peripheral B2M crosses the blood-brain barrier, impacting brain pathology, while its clearance provides neuroprotection. Given current AD treatments' limitations, our findings position B2M as a promising novel therapeutic target, potentially transforming AD intervention strategies.
代表性论文:
1. Gao Y, Hong Y, Huang L, Zheng S, Zhang H, Wang S, Yao Y, Zhao Y, Zhu L, Xu Q, Chai X, Zeng Y, Zeng Y, Zheng L, Zhou Y, Luo H, Zhang X, Zhang H, Zhou Y, Fu G, Sun H, Huang TY, Zheng Q, Xu H, Wang X. β2-microglobulin functions as an endogenous NMDAR antagonist to impair synaptic function. Cell. 2023;186(5):1026-1038.
2. Zhao Y, Zheng Q, Hong Y, Gao Y, Hu J, Lang M, Zhang H, Zhou Y, Luo H, Zhang X, Sun H, Yan XX, Huang TY, Wang YJ, Xu H, Liu C, Wang X. β2-microglobulin coaggregates with Aβ and contributes to amyloid pathology and cognitive deficits in Alzheimer’s disease model mice. Nat Neurosci. 2023. 2023;26(7):1170-1184.
3. Zheng Q, Song B, Li G, Cai F, Wu M, Zhao Y, Jiang L, Guo T, Shen M, Hou H, Zhou Y, Zhao Y, Di A, Zhang L, Zeng F, Zhang X-F, Luo H, Zhang X, Zhang H, Zeng Z, Huang T, Dong C, Qing H, Zhang Y, Zhang Q, Wang X, Wu Y, Xu H, Song W, and Wang X. USP25 inhibition ameliorates Alzheimer’s pathology through regulating APP processing and Aβ generation. J Clin Invest. 2022;132(5): e15217