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In ALS, glutamate homeostasis is dysregulated and glutamate-mediated excitotoxicity is regarded as the key mechanism of ALS pathogenesis (20)

Glucocorticoids can suppress glycolysis by blocking the transcriptional and post-translational effects of hypoxia-inducible factor 1 (HIF-1) in macrophages, while promoting glutamine metabolism to enhance TCA cycle flux and succinate metabolism, thereby preventing intracellular succinate accumulation and facilitating the conversion of macrophages from the M1 to the M2 phenotype (112, 113)

Immune Dysregulation: Damaged mitochondria activate inflammatory pathways, including NLRP3 inflammasome and cGAS-STING, worsening immune imbalances

high levels of oxidative stress may lead to immune evasion, protecting tumor cells from immune system attacks