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Bach1 derepression is neuroprotective in a mouse model of Parkinson's disease

The Keap1-Nrf2 signaling pathway is a promising therapeutic target for Parkinson’s disease (PD). Canonical Nrf2 activators targeting Keap1 thiols are known to be preventive but never effectively cure chronic neurodegeneration because of their electrophilic nature, resulting in nonspecific reactions with active cysteine residues in a variety of cellular proteins. We show that genetic and pharmacologic inhibition of the Nrf2 repressor Bach1 in a posttreatment regimen of experimental PD is neuroprotective by up-regulating Bach1-targeted pathways involving both Nrf2-dependent antioxidant response element (ARE) and non-ARE genes. Inhibition of Bach1 by a nonelectrophilic substituted benzimidazole is a promising therapeutic approach for PD. ....

United States , Johns Hopkins University , Tissue Bank , University Of Maryland Brain , University Of Maryland , Department Of Pharmaceutical Sciences , International Institute For Nanotechnology , Terrance Kavanagh University Of Washington , University Of Buffalo , Parkinson Foundation , Russian Scientific Foundation Grant No , Wenbo Zhi Augusta University , Research Center At Northwestern University , Roland Wolf University Of Dundee , Michaelj Fox Foundation For Parkinson , Curt Freed University Of Colorado , Canonical Nrf , Maryland Brain , Gene Expression Omnibus , Russian Scientific Foundation Grant , Higher School , Economics University Basic Research , Integrated Molecular Structure Education , Research Center , Northwestern University , Hybrid Nanotechnology Experimental Resource ,