香港科技大学宣布,该校晨兴生命科学教授兼香港神经退行性疾病中心主任叶玉如领导的国际研究团队近日发现了一种血液蛋白,在阿尔茨海默病的发病机制中起关键作用,这有助设计创新治疗策略,降低发病风险和改善患者病况。
该项研究发现,随着年龄增长,血液和大脑中的可溶性ST2蛋白含量增加,会扰乱细胞因子白介素33的功效,降低小胶质细胞清除淀粉样蛋白斑的能力,导致淀粉样蛋白斑累积。
团队的发现揭示降低可溶性ST2蛋白水平是治疗阿尔茨海默病的一种方法,有助研发创新治疗策略。叶玉如说,这次研究进一步提高了科学家对阿尔茨海默病发病机制的理解,并为新药开发提供了重要靶点。团队下一步将开发针对可溶性ST2蛋白的临床干预措施,评估其在预防和治疗阿尔茨海默病方面的可行性。
该研究成果近日在《Nature Aging》上发表。
论文原文链接
附论文摘要:
Changes in the levels of circulating proteins are associated with Alzheimer’s disease (AD), whereas their pathogenic roles in AD are unclear. Here, we identified soluble ST2 (sST2), a decoy receptor of interleukin-33–ST2 signaling, as a new disease-causing factor in AD. Increased circulating sST2 level is associated with more severe pathological changes in female individuals with AD. Genome-wide association analysis and CRISPR–Cas9 genome editing identified rs1921622, a genetic variant in an enhancer element of IL1RL1, which downregulates gene and protein levels of sST2. Mendelian randomization analysis using genetic variants, including rs1921622, demonstrated that decreased sST2 levels lower AD risk and related endophenotypes in females carrying the Apolipoprotein E (APOE)-ε4 genotype; the association is stronger in Chinese than in European-descent populations. Human and mouse transcriptome and immunohistochemical studies showed that rs1921622/sST2 regulates amyloid-beta (Aβ) pathology through the modulation of microglial activation and Aβ clearance. These findings demonstrate how sST2 level is modulated by a genetic variation and plays a disease-causing role in females with AD.
参考资料:
《中国科学报》2022-09-01 第1版
港科大发现血液蛋白新靶点 为治疗阿尔茨海默病提供新方向_新华网