2025/01/01 by Zuzana Šmahelová, Lucie Svobodová, Jindřich Sedláček +5 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Insect Resistance and Genetics
paper · pdf · doi:10.1039/d5md00584a
openalex publication_date 2025/01/01 · openalex created_date 2025/10/24 · openalex updated_date 2026/07/02
, 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.