Antitumour drugs targeting tau R3 VQIVYK and Cys322 prevent seeding of endogenous tau aggregates by exogenous seeds

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989100%3A27740%2F22%3A10249003" target="_blank" >RIV/61989100:27740/22:10249003 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15110/22:73610036 RIV/61989592:15310/22:73610036 RIV/61989592:15640/22:73610036

Result on the web

<a href="https://doi.org/10.1111/febs.16270" target="_blank" >https://doi.org/10.1111/febs.16270</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/febs.16270" target="_blank" >10.1111/febs.16270</a>

Result language

angličtina

Original language name

Antitumour drugs targeting tau R3 VQIVYK and Cys322 prevent seeding of endogenous tau aggregates by exogenous seeds

Original language description

Emerging experimental evidence suggests tau pathology spreads between neuroanatomically connected brain regions in a prion-like manner in Alzheimer&apos;s disease (AD). Tau seeding, the ability of prion-like tau to recruit and misfold naïve tau to generate new seeds, is detected early in human AD brains before the development of major tau pathology. Many antitumour drugs have been reported to confer protection against neurodegeneration, supporting the repurposing of approved and experimental or investigational oncology drugs for AD therapy. In this study, we evaluated whether antitumour drugs that abrogate the generation of seed-competent aggregates of tau Repeat 3 (R3) domain peptides can prevent tau seeding and toxicity in Tau-RD P301S FRET Biosensor cells and Caenorhabditis elegans. We demonstrate that drugs that interact with the N-terminal VQIVYK or the C-terminal region housing the Cys322 prevent R3 dimerisation, abolishing the generation of prion-like R3 seeds. Preformed R3 seeds (fibrils) capped with, or R3 seeds formed in the presence of VQIVYK- or Cys322-targeting drugs have a reduced potency to cause aggregation of naïve tau in biosensor cells and protect worms from aggregate toxicity. These findings indicate that VQIVYK- or Cys322-targeting drugs may act as prophylactic agents against tau seeding. (C) 2021 Federation of European Biochemical Societies

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

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

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

FEBS Journal

ISSN

1742-464X

e-ISSN

1432-1033

Volume of the periodical

289

Issue of the periodical within the volume

7

Country of publishing house

US - UNITED STATES

Number of pages

21

Pages from-to

"1929 "- 1949

UT code for WoS article

000719910700001

EID of the result in the Scopus database

2-s2.0-85119193151