Alzheimer's Disease as a Membrane Dysfunction Tauopathy? New Insights into the Amyloid Cascade Hypothesis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F24%3A43927538" target="_blank" >RIV/00064173:_____/24:43927538 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10484717 RIV/00216208:11120/24:43927538 RIV/00064190:_____/24:10001320 RIV/00064165:_____/24:10484717

Výsledek na webu

<a href="https://doi.org/10.3390/ijms25179689" target="_blank" >https://doi.org/10.3390/ijms25179689</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms25179689" target="_blank" >10.3390/ijms25179689</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Alzheimer's Disease as a Membrane Dysfunction Tauopathy? New Insights into the Amyloid Cascade Hypothesis

Popis výsledku v původním jazyce

The amyloid cascade hypothesis postulates that extracellular deposits of amyloid β (Aβ) are the primary and initial cause leading to the full development of Alzheimer&apos;s disease (AD) with intracellular neurofibrillary tangles; however, the details of this mechanism have not been fully described until now. Our preliminary data, coming from our day-to-day neuropathology practice, show that the primary location of the hyperphosphorylated tau protein is in the vicinity of the cell membrane of dystrophic neurites. This observation inspired us to formulate a hypothesis that presumes an interaction between low-density lipoprotein receptor-related protein 1 (LRP1) and fibrillar aggregates of, particularly, Aβ(42) anchored at the periphery of neuritic plaques, making internalization of the LRP1-Aβ(42) complex infeasible and, thus, causing membrane dysfunction, leading to the tauopathy characterized by intracellular accumulation and hyperphosphorylation of the tau protein. Understanding AD as a membrane dysfunction tauopathy may draw attention to new treatment approaches not only targeting Aβ(42) production but also, perhaps paradoxically, preventing the formation of LRP1-Aβ(42).

Název v anglickém jazyce

Alzheimer's Disease as a Membrane Dysfunction Tauopathy? New Insights into the Amyloid Cascade Hypothesis

Popis výsledku anglicky

The amyloid cascade hypothesis postulates that extracellular deposits of amyloid β (Aβ) are the primary and initial cause leading to the full development of Alzheimer&apos;s disease (AD) with intracellular neurofibrillary tangles; however, the details of this mechanism have not been fully described until now. Our preliminary data, coming from our day-to-day neuropathology practice, show that the primary location of the hyperphosphorylated tau protein is in the vicinity of the cell membrane of dystrophic neurites. This observation inspired us to formulate a hypothesis that presumes an interaction between low-density lipoprotein receptor-related protein 1 (LRP1) and fibrillar aggregates of, particularly, Aβ(42) anchored at the periphery of neuritic plaques, making internalization of the LRP1-Aβ(42) complex infeasible and, thus, causing membrane dysfunction, leading to the tauopathy characterized by intracellular accumulation and hyperphosphorylation of the tau protein. Understanding AD as a membrane dysfunction tauopathy may draw attention to new treatment approaches not only targeting Aβ(42) production but also, perhaps paradoxically, preventing the formation of LRP1-Aβ(42).

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30109 - Pathology

Projekt

<a href="/cs/project/NU23-04-00173" target="_blank" >NU23-04-00173: Využití metody RT-QuIC pro zpřesnění diagnostiky neurodegenerativních onemocnění: Prospektivní a retrospektivní studie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

International Journal of Molecular Sciences

ISSN

1661-6596

e-ISSN

1422-0067

Svazek periodika

25

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

9

Strana od-do

9689

Kód UT WoS článku

001310889100001

EID výsledku v databázi Scopus

2-s2.0-85204022729