Intrinsic aggregation and propagation of unmodified tau peptides: R2R3 as a minimal model system

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F25%3A73631230" target="_blank" >RIV/61989592:15640/25:73631230 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15110/25:73631230
Result on the web
<a href="https://www.sciencedirect.com/science/article/abs/pii/S0006349525003698?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0006349525003698?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bpj.2025.06.009" target="_blank" >10.1016/j.bpj.2025.06.009</a>

Result language
angličtina
Original language name
Intrinsic aggregation and propagation of unmodified tau peptides: R2R3 as a minimal model system
Original language description
Tau aggregation into neurofibrillary tangles is a defining feature of Alzheimer's disease and other tauopathies. Although aggregation depends largely on specific amyloidogenic motifs (particularly VQIINK and VQIVYK) in repeated regions of tau microtubule-binding domains, how the primary sequence of adjacent repeats intrinsically influences aggregation and prion-like propagation remains unclear. This study systematically characterized three unmodified, physiologically relevant tau peptide constructs—R1R3, R2R3, and R3R4—to define their intrinsic aggregation kinetics, structural features, and prion-like seeding activity. Among these constructs, we found that R2R3 showed rapid aggregation, distinct β-sheet formation, and potent seeding capable of sustained secondary propagation in cellular biosensor assays. Whereas recent studies have highlighted chemically modified peptides (e.g., acetylated and phosphomimic peptides), our study emphasizes the importance of native, unmodified sequences as fundamental determinants in tau aggregation. Furthermore, these findings establish R2R3 as a robust minimal tau model, providing a valuable tool for mechanistic research and therapeutic screening in tau-related neurodegeneration.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10610 - Biophysics

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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