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

Result code in 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>
Alternative codes found
RIV/00216208:11310/25:10504805
Result on the web
<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>

Result language
angličtina
Original language name
Investigating NFE2L1 activators for targeted protein aggregate clearance: a follow-up study
Original language description
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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30107 - Medicinal chemistry

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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