Early but not late conformational changes of tau in association with ubiquitination of neurofibrillary pathology in Alzheimer’s disease brains

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F20%3A43920444" target="_blank" >RIV/00023752:_____/20:43920444 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0006899320303097?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0006899320303097?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.brainres.2020.146953" target="_blank" >10.1016/j.brainres.2020.146953</a>

Result language

angličtina

Original language name

Early but not late conformational changes of tau in association with ubiquitination of neurofibrillary pathology in Alzheimer’s disease brains

Original language description

In Alzheimer&apos;s disease, tau protein undergoes post-translational modifications including hyperphosphorylation and truncation, which promotes two major conformational changes associated with progressive N-terminal folding. Along with the development of the disease, tau ubiquitination was previously shown to emerge in the early and intermediate stages of the disease, which is closely associated with early tau truncation at aspartic acid 421, but not with a subsequently truncated tau molecule at glutamic acid 391. In the same group of cases, using multiple immunolabeling and confocal microscopy, a possible relationship between the ubiquitin-targeting of tau and the progression of conformational changes adopted by the N-terminus of this molecule was further studied. A comparable number of neurofibrillary tangles was found displaying ubiquitin, an early conformation recognized by the Alz-50 antibody, and a phosphorylation. However, a more reduced number of neurofibrillary tangles were immunoreactive to Tau-66 antibody, a late tau conformational change marker. When double-labeling profiles of neurofibrillary tangles were assessed, ubiquitination was clearly demonstrated in tau molecules undergoing early N-terminal folding, but was barely observed in late conformational changes of the N-terminus adopted by tau. The same pattern of colocalization was visualized in neuritic pathology. Overall, these results indicate that a more intact conformation of the N-terminus of tau may facilitate tau ubiquitination, but this modification may not occur in a late truncated and more compressed folding of the N-terminus of the tau molecule.

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

30103 - Neurosciences (including psychophysiology)

Project

<a href="/en/project/NV16-27611A" target="_blank" >NV16-27611A: Interactions of intracellular amyloid beta and diagnosis of Alzheimer disease</a><br>

Continuities

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

Publication year

2020

Confidentiality

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

Name of the periodical

Brain Research

ISSN

0006-8993

e-ISSN

—

Volume of the periodical

1744

Issue of the periodical within the volume

October

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

10

Pages from-to

146953

UT code for WoS article

000541249900006

EID of the result in the Scopus database

2-s2.0-85086378455