Dong Suwei's team has made progress in the study of glycosylation modification regulation of β amyloid peptide aggregation mechanism

Recently, the academic journal " Journal of the American Chemical Society " published an online publication entitled "O-Glycosylation Induces Amyloid-β to Form New Fibril Polymorphs Vulnerable for Degradation" ( O- glycosylation induces β- amyloid peptides to form new easily degradable fiber aggregates)

The misfolding of amyloid β ( Aβ ) and its accumulation in the brain are thought to be closely related to the occurrence and development of Alzheimer's disease ( AD )

Dongsu Wei team using chemical synthesis strategies with different constructs a series of O- glycosylation (including mucin- mucin representative glycoforms [alpha]-GalNAc , Galβ1-3GalNAc and Neuα2,3Galβ1-3GalNAc uniform structure) of the β starch Based on its system , the regulation of sugar chain on the pathological aggregation of Aβ and its structure-activity relationship have been studied

Exploring the regulation of glycosylation on the biophysical properties of Aβ42 based on chemical synthesis strategies

The author used spectroscopy and electron microscopy to characterize the secondary structure, aggregation properties, and fiber morphology of the three Aβ glycopeptides and the original Aβ polypeptide without sugar chains , and found that glycosylation modification can significantly inhibit the aggregation of Aβ , and As the structure of the sugar chain increases, this inhibitory effect is also enhanced, which reflects that the complexity of the sugar chain structure (including size effects, etc.

In order to further understand the molecular mechanism of glycosylation reducing the stability of Aβ pathological fibers, Dong Suwei’s team worked with Liu Cong’s team at the Intersection Center of Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, and used cryo-electron microscopy to analyze glycoforms with Galβ1-3GalNAc .

This work discovered for the first time the important function of glycosyl modification in dynamically regulating the pathological aggregation of Aβ , and provided favorable research tools and new research for subsequent studies on the biological activity and pathological toxicity of different glycosyl modifications regulating the accumulation of pathological proteins in neurodegenerative diseases.

Group photo of some research team members

From left: Huang Lu, Wei Qijia, Dong Suwei, Liu Dangliang, Zhang Qikai, Wang Xiaoya

This research was funded by the National Natural Science Foundation of China's Major Research Program, the Outstanding Youth Fund, the Key R&D Program of the Ministry of Science and Technology, the Outstanding Youth Fund of the Beijing Municipal Natural Science Foundation, and the Chinese Academy of Sciences' Stable Support for Youth Team Program in Basic Research

Link to the paper : https://pubs.

【Introduction of Researcher Dong Suwei】

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Contributions from the State Key Laboratory of Natural Medicines and Biomimetic Medicines