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通过合成MUC-TypeO-Glycosylated APP Glycopeptides探测APP裂变和氨基酸β组合,通过合成MUC-TypeO-Glycosylated APP Glycopeptides进行探测

Nancy Vela Navarro¹, Gustavo De Nadai Mundim¹, Deepika Regmi¹

¹Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton, Florida 33431, United States.

ACS chemical neuroscience

|February 25, 2026

概括

粉样蛋白前体蛋白 (APP) 的异常O-糖化影响其加工和聚合. 特定位点的糖化和突变改变了粉样β (Aβ) 路径,影响了阿尔茨海默病的发病过程.

科学领域:

生物化学生物化学
分子生物学分子生物学
神经科学是一个神经科学.

背景情况:

粉样蛋白前体蛋白 (APP) 的异常蛋白质分解加工与粉样β (Aβ) 贩运有关.
MUC1型O-糖化被认为是调节APP处理的因素.

研究的目的:

调查特定地点O-糖化和瑞典突变对APP结构,加工和聚合的影响.
阐明Thr663,Ser667和/或Tyr681的糖化如何影响APP的二次结构和分泌酶裂变.

主要方法:

合成本地和瑞典突变的APP糖与O-GalNAc部分.
循环二元化 (CD) 用于形状分析.
对分泌酶 (BACE1和ADAM10) 裂变的分析.
在体外测试 (与Aβ40的共化,ThT动力学,AFM/TEM成像,DLS) 来研究纤维的形成和寡合化.

主要成果:

糖化位点和密度影响了APP构型,增高的价值有利于β转丰富的结构.
瑞典突变增强了BACE1的裂变,特别是通过Ser667的糖化.
额外的甘氨酸将加工转移到ADAM10上,但并没有完全抵消氨基基基因的产生.
赛尔667糖化促进了Aβ40纤维的形成,而二-和三糖化破坏了纤维,有利于寡合体.

结论:

特定位点的糖化和突变极大地影响了APP的蛋白质分解加工和二次结构.
糖化模式影响APP聚合行为,影响纤维结构和寡合体形成.
这些发现对于理解APP在健康和疾病,特别是阿尔茨海默病中的功能至关重要.

关键词:

在AFM和TEM中使用.阿尔茨海默氏症是阿尔茨海默氏症的一种疾病.在MUC类型的糖化化中.聚合方式聚合方式聚合方式蛋白质溶解裂变的发生.

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