Time- and dose-dependent seeding tendency of exogenous tau R2 and R3 aggregates in cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F23%3A73618356" target="_blank" >RIV/61989592:15640/23:73618356 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/23:73618356

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0006291X23002425?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0006291X23002425?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bbrc.2023.02.057" target="_blank" >10.1016/j.bbrc.2023.02.057</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Time- and dose-dependent seeding tendency of exogenous tau R2 and R3 aggregates in cells

Popis výsledku v původním jazyce

Tauopathies are a group of neurodegenerative diseases categorised into three types, 3R, 4R, or 3Rþ4R (mixed) tauopathies, based on the tau isoforms that make up the aberrant filaments. It is supposed that all six tau isoforms share functional characteristics. However, differences in the neuropathological features associated with different tauopathies offer the possibility that disease progression and tau accumulation may vary depending on the isoform composition. The presence or absence of repeat 2 (R2) in the microtubule-binding domain defines the type of isoform, which might influence tau pathology associated with a particular tau isoform. Therefore, our study aimed to identify the differences in the seeding propensities of R2 and repeat 3 (R3) aggregates using HEK293T biosensor cells. We show that the seeding induced by R2 was generally higher than by R3 aggregates, and lower concentrations of R2 aggregates are sufficient to induce seeding. Next, we found that both R2 and R3 aggregates dosedependently increased triton-insoluble Ser262 phosphorylation of native tau, which is only visible in cells seeded with higher concentrations (12.5 nM or 100 nM) of R2 and R3 aggregates, despite the seeding by the lower concentrations of R2 aggregates after 72 h. However, the accumulation of tritoninsoluble pSer262 tau was visible earlier in cells induced with R2 than in R3 aggregates. Our findings suggest that the R2 region may contribute to the early and enhanced induction of tau aggregation and define the difference in disease progression and neuropathology of 4R tauopathies.

Název v anglickém jazyce

Time- and dose-dependent seeding tendency of exogenous tau R2 and R3 aggregates in cells

Popis výsledku anglicky

Tauopathies are a group of neurodegenerative diseases categorised into three types, 3R, 4R, or 3Rþ4R (mixed) tauopathies, based on the tau isoforms that make up the aberrant filaments. It is supposed that all six tau isoforms share functional characteristics. However, differences in the neuropathological features associated with different tauopathies offer the possibility that disease progression and tau accumulation may vary depending on the isoform composition. The presence or absence of repeat 2 (R2) in the microtubule-binding domain defines the type of isoform, which might influence tau pathology associated with a particular tau isoform. Therefore, our study aimed to identify the differences in the seeding propensities of R2 and repeat 3 (R3) aggregates using HEK293T biosensor cells. We show that the seeding induced by R2 was generally higher than by R3 aggregates, and lower concentrations of R2 aggregates are sufficient to induce seeding. Next, we found that both R2 and R3 aggregates dosedependently increased triton-insoluble Ser262 phosphorylation of native tau, which is only visible in cells seeded with higher concentrations (12.5 nM or 100 nM) of R2 and R3 aggregates, despite the seeding by the lower concentrations of R2 aggregates after 72 h. However, the accumulation of tritoninsoluble pSer262 tau was visible earlier in cells induced with R2 than in R3 aggregates. Our findings suggest that the R2 region may contribute to the early and enhanced induction of tau aggregation and define the difference in disease progression and neuropathology of 4R tauopathies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ISSN

0006-291X

e-ISSN

1090-2104

Svazek periodika

653

Číslo periodika v rámci svazku

31.03.2023

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

4

Strana od-do

102-105

Kód UT WoS článku

000949585300001

EID výsledku v databázi Scopus

2-s2.0-85150430796