A novel cellular model for investigating experimental therapy in Alpha-1-antitrypsin deficiency

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F25%3A00085839" target="_blank" >RIV/00023001:_____/25:00085839 - isvavai.cz</a>

Výsledek na webu

—

DOI - Digital Object Identifier

—

Jazyk výsledku

angličtina

Název v původním jazyce

A novel cellular model for investigating experimental therapy in Alpha-1-antitrypsin deficiency

Popis výsledku v původním jazyce

Alpha-1-antitrypsin (A1AT) is a liver-secreted plasma serine protease inhibitor encodedby the SERPINA1 gene. Mutations in SERPINA1 lead to alpha-1-antitrypsin deficiency (AATD),a common genetic disorder affecting the lung and the liver. The most prevalent pathogenic variant,named Z allele (c.1096G&gt;A; p.Glu366Lys), causes misfolding, polymerization and retention ofmutated A1AT in endoplasmic reticulum (ER) of hepatocytes. This results in hepatocellulardamage causing progressive liver disease. BRD4780 has shown therapeutic potential in severalproteinopathies by promoting degradation of misfolded proteins apparently through its interactionwith TMED9 (transmembrane P24 Trafficking Protein 9) positive cargo receptor-containingvesicles, where the protein folding quality control system is present. This study aimed toinvestigate the effect of BRD4780 on mutant Z-A1AT protein clearance using a novel cellularmodel of AATD.

Název v anglickém jazyce

A novel cellular model for investigating experimental therapy in Alpha-1-antitrypsin deficiency

Popis výsledku anglicky

Alpha-1-antitrypsin (A1AT) is a liver-secreted plasma serine protease inhibitor encodedby the SERPINA1 gene. Mutations in SERPINA1 lead to alpha-1-antitrypsin deficiency (AATD),a common genetic disorder affecting the lung and the liver. The most prevalent pathogenic variant,named Z allele (c.1096G&gt;A; p.Glu366Lys), causes misfolding, polymerization and retention ofmutated A1AT in endoplasmic reticulum (ER) of hepatocytes. This results in hepatocellulardamage causing progressive liver disease. BRD4780 has shown therapeutic potential in severalproteinopathies by promoting degradation of misfolded proteins apparently through its interactionwith TMED9 (transmembrane P24 Trafficking Protein 9) positive cargo receptor-containingvesicles, where the protein folding quality control system is present. This study aimed toinvestigate the effect of BRD4780 on mutant Z-A1AT protein clearance using a novel cellularmodel of AATD.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

30219 - Gastroenterology and hepatology

Projekt

<a href="/cs/project/LX22NPO5104" target="_blank" >LX22NPO5104: Národní institut pro výzkum metabolických a kardiovaskulárních onemocnění</a><br>

Návaznosti

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

Rok uplatnění

2025

Kód důvěrnosti údajů

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