Investigating NFE2L1 activators for targeted protein aggregate clearance: a follow-up study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00641439" target="_blank" >RIV/61388963:_____/25:00641439 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/25:10504805

Výsledek na webu

<a href="https://doi.org/10.1039/D5MD00584A" target="_blank" >https://doi.org/10.1039/D5MD00584A</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/D5MD00584A" target="_blank" >10.1039/D5MD00584A</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Investigating NFE2L1 activators for targeted protein aggregate clearance: a follow-up study

Popis výsledku v původním jazyce

Disruption of protein homeostasis (proteostasis), whether by acute proteotoxic stress or chronic expression of mutant proteins, can lead to the accumulation of toxic protein aggregates. Such aggregation is a hallmark of numerous diseases and is often associated with impaired protein clearance mechanisms. The transcription factor nuclear factor erythroid 2-related factor 1 (encoded by NFE2L1, also known as Nrf1) plays a central role in restoring proteostasis by increasing proteasome synthesis. Therefore, pharmacological activation of NFE2L1 under non-stress conditions represents a promising therapeutic strategy for neurodegenerative and other proteostasis-related diseases. In our previous study, we identified bis(phenylmethylene)cycloalkanone derivatives as NFE2L1 activators capable of inducing proteasome subunit expression, increasing heat shock protein levels, and stimulating autophagy. Building upon these findings, we have now developed a new library of structurally related compounds to identify novel more potent NFE2L1 activators. By systematically examining how specific chemical substitutions affect NFE2L1 activation, this work advances our understanding of the structure–activity relationships within this pathway.

Název v anglickém jazyce

Investigating NFE2L1 activators for targeted protein aggregate clearance: a follow-up study

Popis výsledku anglicky

Disruption of protein homeostasis (proteostasis), whether by acute proteotoxic stress or chronic expression of mutant proteins, can lead to the accumulation of toxic protein aggregates. Such aggregation is a hallmark of numerous diseases and is often associated with impaired protein clearance mechanisms. The transcription factor nuclear factor erythroid 2-related factor 1 (encoded by NFE2L1, also known as Nrf1) plays a central role in restoring proteostasis by increasing proteasome synthesis. Therefore, pharmacological activation of NFE2L1 under non-stress conditions represents a promising therapeutic strategy for neurodegenerative and other proteostasis-related diseases. In our previous study, we identified bis(phenylmethylene)cycloalkanone derivatives as NFE2L1 activators capable of inducing proteasome subunit expression, increasing heat shock protein levels, and stimulating autophagy. Building upon these findings, we have now developed a new library of structurally related compounds to identify novel more potent NFE2L1 activators. By systematically examining how specific chemical substitutions affect NFE2L1 activation, this work advances our understanding of the structure–activity relationships within this pathway.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

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

RSC Medicinal Chemistry

ISSN

2632-8682

e-ISSN

2632-8682

Svazek periodika

16

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

15

Strana od-do

6397-6411

Kód UT WoS článku

001634773300001

EID výsledku v databázi Scopus

2-s2.0-105024408649