Modulation of Amyloid-β Aggregation by Surface Proteins from Pathogens Associated with Alzheimer's Disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F25%3A00639190" target="_blank" >RIV/60077344:_____/25:00639190 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00159816:_____/25:00082334 RIV/00216224:14310/25:00142063 RIV/00027162:_____/25:N0000090

Výsledek na webu

<a href="https://doi.org/10.1021/acschemneuro.5c00444" target="_blank" >https://doi.org/10.1021/acschemneuro.5c00444</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acschemneuro.5c00444" target="_blank" >10.1021/acschemneuro.5c00444</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Modulation of Amyloid-β Aggregation by Surface Proteins from Pathogens Associated with Alzheimer's Disease

Popis výsledku v původním jazyce

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder. Despite substantial research efforts, our understanding of its pathogenesis remains incomplete, limiting the development of effective treatments and preventive strategies. The potential role of microbial pathogens in AD etiology has gained increasing attention. Various human microbial pathogens have been identified in the brains of AD patients, leading to the pathogen hypothesis, which posits that these microorganisms may disrupt the brain's immune regulation and homeostasis. In this study, we examine the effects of proteins from three pathogens, Borrelia burgdorferi, HSV-1, and Porphyromonas gingivalis, on the aggregation of antimicrobial peptide amyloid-beta (A beta). Three of the four studied proteins were found to attenuate the aggregation of A beta 42 by interacting with its soluble form and inhibiting primary and secondary pathways. These in vitro findings were further supported by experiments using mature neurons derived from human pluripotent stem cells, which showed an increased accumulation of amyloid precursor protein (APP) aggregates upon infection with HSV-1 or exposure to the OspA surface protein from B. burgdorferi. Together, our results provide mechanistic insights into how pathogen-associated proteins modulate A beta 42 aggregation, contributing to an understanding of their potential role in AD pathogenesis.

Název v anglickém jazyce

Modulation of Amyloid-β Aggregation by Surface Proteins from Pathogens Associated with Alzheimer's Disease

Popis výsledku anglicky

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder. Despite substantial research efforts, our understanding of its pathogenesis remains incomplete, limiting the development of effective treatments and preventive strategies. The potential role of microbial pathogens in AD etiology has gained increasing attention. Various human microbial pathogens have been identified in the brains of AD patients, leading to the pathogen hypothesis, which posits that these microorganisms may disrupt the brain's immune regulation and homeostasis. In this study, we examine the effects of proteins from three pathogens, Borrelia burgdorferi, HSV-1, and Porphyromonas gingivalis, on the aggregation of antimicrobial peptide amyloid-beta (A beta). Three of the four studied proteins were found to attenuate the aggregation of A beta 42 by interacting with its soluble form and inhibiting primary and secondary pathways. These in vitro findings were further supported by experiments using mature neurons derived from human pluripotent stem cells, which showed an increased accumulation of amyloid precursor protein (APP) aggregates upon infection with HSV-1 or exposure to the OspA surface protein from B. burgdorferi. Together, our results provide mechanistic insights into how pathogen-associated proteins modulate A beta 42 aggregation, contributing to an understanding of their potential role in AD pathogenesis.

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

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

ACS Chemical Neuroscience

ISSN

1948-7193

e-ISSN

1948-7193

Svazek periodika

16

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

3554-3566

Kód UT WoS článku

001559032300001

EID výsledku v databázi Scopus

2-s2.0-105016491011