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@ARTICLE{Chakraborty:274063,
author = {Chakraborty, Pijush and Ibáñez de Opakua, Alain and
Purslow, Jeffrey and Fromm, Simon A and Chatterjee, Debdeep
and Zachrdla, Milan and Zhuang, Shannon and Puri, Sambhavi
and Wolozin, Benjamin and Zweckstetter, Markus},
title = {{GSK}3β phosphorylation catalyzes the aggregation of tau
into {A}lzheimer's disease-like filaments.},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {121},
number = {52},
issn = {0027-8424},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {DZNE-2025-00044},
pages = {e2414176121},
year = {2024},
abstract = {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.},
keywords = {tau Proteins: metabolism / Alzheimer Disease: metabolism /
Alzheimer Disease: pathology / Phosphorylation / Humans /
Glycogen Synthase Kinase 3 beta: metabolism / Protein
Aggregation, Pathological: metabolism / Protein Processing,
Post-Translational / Brain: metabolism / Brain: pathology /
Cryoelectron Microscopy / Protein Aggregates / Alzheimer's
disease (Other) / NMR (Other) / cryo-EM (Other) /
phosphorylation (Other) / tau (Other) / tau Proteins (NLM
Chemicals) / Glycogen Synthase Kinase 3 beta (NLM Chemicals)
/ MAPT protein, human (NLM Chemicals) / Protein Aggregates
(NLM Chemicals) / GSK3B protein, human (NLM Chemicals)},
cin = {AG Zweckstetter},
ddc = {500},
cid = {I:(DE-2719)1410001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39693350},
pmc = {pmc:PMC11670061},
doi = {10.1073/pnas.2414176121},
url = {https://pub.dzne.de/record/274063},
}