Implications of Nicotinamide Adenine Dinucleotide Reductive Stress in Health and Diseases- A Narrative Review

Nicotinamide Adenine Dinucleotide (NAD+) takes part in cellular energy metabolism by accepting hydride equivalents to form reduced NADH, which furnishes reducing equivalents to mitochondrial Electron Transport Chain (ETC). Usually, NADH (H for hydrogen)/NAD+ (redox couple is crucial for cellular redox homeostasis and healthy physiological condition. Reductive Stress (RS) denotes a stable alteration of redox homeostasis due to overexpression of the antioxidant enzyme system, which could deplete Reactive Oxygen Species (ROS). This might potentially switch the redox couple from an oxidative state to a reduced state. Notably, it navigates the cell to RS. Emerging evidence recommends that RS might be even more detrimental than its counterpart oxidative stress. Contemporary perception on fundamental mechanisms of RS, due to perturbation of redox couple, is limited. This review is based on recent comprehension on the biochemical and metabolic role of NADH/NAD+ redox couple and its title role in promoting diseases like cancer, cardiovascular disease, Diabetes Mellitus (DM), neurodegenerative diseases. Besides, insight into the evolution of NAD+ redox signaling will augment the perspective on cellular redox homeostasis. Upcoming coveted analyses are desired to establish and explore metabolic transformation to RS. Moreover, the anti-reductant approach to hinder RS will be noteworthy.