肌萎缩侧索硬化症患者血液外泌体的苏木化修饰研究OA
SUMOylation of Blood Exosomes in Amyotrophic Lateral Sclerosis
肌萎缩侧索硬化症(ALS)临床诊断缺乏早期标志物,外周血成分复杂,难以直接反映病理变化.血液外泌体作为稳定携带源细胞蛋白信息的纳米囊泡,为无创疾病监测提供了窗口.苏木化修饰(SUMOylation)是重要的翻译后修饰,在疾病中起关键调控作用,但SUMO-1修饰在ALS血液外泌体中的特征尚不明确.该研究基于噬菌体展示技术筛选亲和配体(CP-1)并合成特异性富集材料(M2),结合液相色谱-串联质谱,对4例早期和4例中晚期ALS患者血液外泌体进行SUMO-1修饰蛋白质组学分析.共鉴定到119个SUMO-1修饰蛋白,中晚期患者修饰蛋白的整体丰度显著高于早期患者,且主要富集于趋化因子及HIF-1信号通路,提示外泌体SUMO-1修饰可能参与ALS病理过程,为疾病机制研究提供了新线索.
The clinical diagnosis of ALS lacks early biomarkers,and the complexity of peripheral blood components makes it difficult to directly reflect pathological changes.Blood exosomes,which stably carry protein information from their source cells,provide a window for non-invasive disease monitoring.SUMOylation is a crucial post-translational modification that plays a key regulatory role in disease.However,the characteristics of SUMO-1 modification in the blood exosomes of ALS pa‑tients remain unclear.To address this,this study utilized an affinity ligand(CP-1)screened via phage display technology to synthesize a specific enrichment material(M2).Combined with LC-MS/MS,a proteomic analysis of SUMO-1 modifications was performed on blood exosomes from 4 early-stage and 4 mid-to-late-stage ALS patients.A total of 119 SUMO-1-modified proteins were identi‑fied.The overall abundance of these modified proteins was significantly higher in middle-to-late-stage patients compared to early-stage patients,and they were primarily enriched in the chemokine signal‑ing and HIF-1 signaling pathways.These findings suggest that exosomal SUMO-1 modification may be involved in the pathological process of ALS,providing new clues for understanding the disease mechanism.
周凌竹;王存利;张晓雨;宋艳玲;卿光焱
沈阳化工大学 化学工程学院,辽宁 沈阳 110142中国科学院大连化学物理研究所 中药科学研究中心,辽宁 大连 116023中国科学院大连化学物理研究所 中药科学研究中心,辽宁 大连 116023沈阳化工大学 化学工程学院,辽宁 沈阳 110142中国科学院大连化学物理研究所 中药科学研究中心,辽宁 大连 116023
化学化工
肌萎缩侧索硬化症外泌体苏木化修饰噬菌体筛选液相色谱-串联质谱
amyotrophic lateral sclerosisexosomesSUMOylationphage displayLC-MS/MS
《分析测试学报》 2026 (5)
922-928,7
国家自然科学基金项目(22504140)
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