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Pharmacological targeting of CHAC1-mediated processes therefore represents a rational therapeutic strategy, potentially disrupting the cycle of GSH depletion, ER stress amplification and iron-dependent peroxidation that drives neuronal loss

Generation of CRISPR KO strains To generate a knockout of glutathione reductase (GSR) in HEK293 cells, a guide RNA sequence targeting exon 1 was cloned into the pSpCas9(BB)-2A-GFP (PX458) vector, gifted from Feng Zhang (Addgene plasmid #48138, Watertown, MA, United States) 84

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As many ERK5 kinase inhibitors have limited effectiveness, a strategy for inducing ERK5 degradation has been developed

Primary osteoarthritis chondrocyte map of chromatin conformation reveals novel candidate effector genes

doi: 10.1038/s41584-025-01223-y 2 GBD 2021 Osteoarthritis Collaborators