GSK3β phosphorylation catalyzes the aggregation of tau into Alzheimer's disease- like filaments

• 成果类型: Article
• 署名作者: Chakraborty, Pijush; Purslow, Jeffrey A.; Fromm, Simon A.; Chatterjee, Debdeep; Zachrdla, Milan; Zhuang, Shannon; Puri, Sambhavi; Wolozin, Benjamin; Zweckstetter, Markus
• 署名单位: Helmholtz Association; German Center for Neurodegenerative Diseases (DZNE); European Molecular Biology Laboratory (EMBL); Boston University; Boston University; Boston University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14832
• DOI: 10.1073/pnas.2414176121
• 发表日期: 2024-12-24
• 关键词: paired helical filaments; glycogen-synthase kinase-3; protein; gsk-3-beta; brain; core

摘要

The pathological deposition of proteins is a hallmark of several devastating neurodegenerative diseases. These pathological deposits comprise aggregates of proteins that adopt distinct structures named strains. However, the molecular factors responsible for the formation of distinct aggregate strains are unknown. Here, we show that the serine/ by several other kinases, promotes the aggregation of full- length tau as well as enhances reveals that the fibrils formed by GSK3(3- phosphorylated tau adopt a fold comparable to that of paired helical filaments isolated from the brains of AD patients. Our results elucidate the intricate relationship between posttranslational modification and the formation of tau strains in neurodegenerative diseases.