Redox molecules in health and disease-then and now

Redox biology can be defined as the total sum of all oxidation and reduction reactions occurring in a healthy cell. Cellular homeostasis is maintained by a group of molecules viz. NADP: NADPH; GSH: GSSG; GSH dependent enzymes, hypoxia inducible factor; nuclear factorKB; MAP kinases and aryl hydrocarbon receptors. However, several stimuli/ factors like drugs, chemicals, pathogens, xenobiotics and diseases can disrupt the redox control over the cell leading to oxidative or nitrosative stress. Functions of redox molecules are governed through a redox code. Integrated groups of GSTome, seleno-cysteine-proteome and redox couples constitute a redoxosome, and their functions are regulated by a couple of redox switches. These redox switches determine cellular homeostasis and are controlled by redox check points like GSH, TRx, caspase-9 and 3, MLKL, GSDMD, GPx and MOMP. It is assumed that the nature of stimulus, cell type and hierarchy of inter-organelle cross talk(s) might result into different modalities of cell death under the shared network of redox signaling pathways. Recently, a few redox responsive systems have been developed. These include a high concentration of ROS and glutathione that are characterstic of tumor microenvironment (TME). Redox responsive nanoparticles include GSH responsive disulfide, ROS responsive thioketal, arylboronic ester, bilirubin as well as GSH/ROS dual responsive diselenide and dicarbonyl thioethers. Redox switches offer answers to many biological paradigms. Present review is an attempt to summarize the available information on molecular players of redox biology. Further, the role of redox system in human diseases viz. ageing, fibrosis, cancer, cardiovascular and neuro-degenerative diseases has also been discussed. Benchmark investigations made in redox biology may be translated into a new discipline of redox medicine in near future.