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001     274063
005     20250119000314.0
024 7 _ |a 10.1073/pnas.2414176121
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037 _ _ |a DZNE-2025-00044
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082 _ _ |a 500
100 1 _ |a Chakraborty, Pijush
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245 _ _ |a GSK3β phosphorylation catalyzes the aggregation of tau into Alzheimer's disease-like filaments.
260 _ _ |a Washington, DC
|c 2024
|b National Acad. of Sciences
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520 _ _ |a 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/threonine kinase GSK3β catalyzes the aggregation of the protein tau into Alzheimer's disease (AD)-like filaments. We demonstrate that phosphorylation by GSK3β, but not by several other kinases, promotes the aggregation of full-length tau as well as enhances phase separation into gel-like condensate structures. Cryoelectron microscopy further reveals that the fibrils formed by GSK3β-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.
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650 _ 7 |a Alzheimer's disease
|2 Other
650 _ 7 |a NMR
|2 Other
650 _ 7 |a cryo-EM
|2 Other
650 _ 7 |a phosphorylation
|2 Other
650 _ 7 |a tau
|2 Other
650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 7 |a Glycogen Synthase Kinase 3 beta
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 7 |a MAPT protein, human
|2 NLM Chemicals
650 _ 7 |a Protein Aggregates
|2 NLM Chemicals
650 _ 7 |a GSK3B protein, human
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 2 |a tau Proteins: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Phosphorylation
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Glycogen Synthase Kinase 3 beta: metabolism
|2 MeSH
650 _ 2 |a Protein Aggregation, Pathological: metabolism
|2 MeSH
650 _ 2 |a Protein Processing, Post-Translational
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Cryoelectron Microscopy
|2 MeSH
650 _ 2 |a Protein Aggregates
|2 MeSH
700 1 _ |a Ibáñez de Opakua, Alain
|0 P:(DE-2719)2812657
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700 1 _ |a Purslow, Jeffrey
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700 1 _ |a Fromm, Simon A
|0 0000-0002-2094-1911
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700 1 _ |a Chatterjee, Debdeep
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700 1 _ |a Zachrdla, Milan
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700 1 _ |a Zhuang, Shannon
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700 1 _ |a Puri, Sambhavi
|0 0009-0003-1991-3977
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700 1 _ |a Wolozin, Benjamin
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700 1 _ |a Zweckstetter, Markus
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773 _ _ |a 10.1073/pnas.2414176121
|g Vol. 121, no. 52, p. e2414176121
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|t Proceedings of the National Academy of Sciences of the United States of America
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856 4 _ |y OpenAccess
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