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Indeed, there is evidence that ATF4 can bind to the amino acid response element in the promoters of genes such as CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) and asparagine synthetase, thereby up-regulating their expression ( Reference Kilberg, Pan and Chen 54 , Reference Averous, Bruhat and Jousse 62 )

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Emerging Strategies include metabolic modulation (e.g., IGF1R inhibitors reducing glycolysis in Graves’ Orbitopathy fibroblasts) and selective ferroptosis induction in pathogenic cells (e.g., IKE targeting synovial fibroblasts in RA)