KEAP1 covalent modifier with therapeutic potential for Huntington′s disease by promoting NRF2 activation.
MIND4-17 is a potent NRF2 (nuclear factor erythroid 2-related factor 2) activator that covalently modifies a critical stress-sensor cysteine (C151) in the BTB domain of the E3 ligase substrate adaptor protein Kelch-like ECH-associated protein 1 (KEAP1), the primary negative regulator of NRF2. MIND4-17 induces NRF2 activation responses in neuronal and non-neuronal cultures (effective conc. 0.1-10 μM) of human, mouse, and rat origins. In addition, MIND4-17 effectively reduces endotoxin-induced IL-6 release from WT as well as YAC128 HD mutant mice-derived primary microglia and astrocytes, however, NRF2 induction by MIND4-17 is shown to be compromised in human Huntington′s diseased (HD) relative to non-disesed neural stem cells due to suppressive influence of the expanded CAG repeat mutation on pathway activation.
Cell chemical biology, 23(7), 849-861 (2016-07-19)
There are currently no disease-modifying therapies for the neurodegenerative disorder Huntington's disease (HD). This study identified novel thiazole-containing inhibitors of the deacetylase sirtuin-2 (SIRT2) with neuroprotective activity in ex vivo brain slice and Drosophila models of HD. A systems biology approach
Proceedings of the National Academy of Sciences of the United States of America, 114(23), E4676-E4685 (2017-05-24)
The activity of the transcription factor nuclear factor-erythroid 2 p45-derived factor 2 (NRF2) is orchestrated and amplified through enhanced transcription of antioxidant and antiinflammatory target genes. The present study has characterized a triazole-containing inducer of NRF2 and elucidated the mechanism
Questions
Reviews
★★★★★ No rating value
Active Filters
Notre équipe de scientifiques dispose d'une expérience dans tous les secteurs de la recherche, notamment en sciences de la vie, science des matériaux, synthèse chimique, chromatographie, analyse et dans de nombreux autres domaines..
