Fig. 2
From: Redox dysregulation as a driver for DNA damage and its relationship to neurodegenerative diseases
Mechanisms involved in maintaining cellular redox homeostasis. The cellular redox state is a sensitive balance between oxidation and reduction reactions, involving the production of free radicals and the antioxidant systems that neutralize them. H2O2 is generated by SOD enzymes CuZnSOD in the cytoplasm, and it also enters the cell from the extracellular space, which together enhance intracellular H2O2 levels. H2O2 can be safely decomposed by catalase into water (H2O) and oxygen (O2). The mitochondrial enzyme MnSOD also has dismutase activity, which detoxifies the free radical O2·− generated by mitochondrial respiration. The cellular redox state is regulated by the thioredoxin (Trx/TrxR) and glutaredoxins (Grx) systems, which modifies specific redox-sensitive proteins, thereby triggering related signalling events. The nuclear factor erythroid 2-related factor 2 (Nrf2) system is then activated, leading to an antioxidant response. The NADPH oxidase complex is inactive under normal circumstances but is activated during respiratory burst. Glutaredoxin 4 (GPx4) reduces lipid hydroxide (LOOH) to alcohol (LOH). GR glutathione reductase, NF-κB nuclear factor kappa B, NOS nitric oxide synthase, NADPH nicotinamide adenine dinucleotide phosphate