Nampt: a new therapeutic target for modulating NAD levels in metabolic, cardiovascular, and neurodegenerative diseases.

NAD is an important cofactor involved in regulating many biochemical processes in cells. An imbalance in NAD/NADH ratio is linked to many diseases. NAD is depleted in diabetes, cardiovascular and neurodegenerative diseases, and in aging, and is increased in tumor cells. NAD is generated in cells via the de novo, Preiss-Handler, and salvage pathways. Most of the cellular NAD is generated through Nampt activation, a key rate-limiting enzyme that is involved in the salvage pathway. Restoration of NAD/NADH balance offers therapeutic advantages for improving tissue homeostasis and function. NAD is known to benefit and restore the body's physiological mechanisms, including DNA replication, chromatin and epigenetic modifications, and gene expression. Recent studies elucidate the role of NAD in cells utilizing transgenic mouse models. Translational new therapeutics are positioned to utilize the NAD restoration strategies for overcoming the drawbacks that exist in the pharmacological toolkit. The present review highlights the significance of Nampt-NAD axis as a major player in energy metabolism and provides an overview with insights into future strategies, providing pharmacological advantages to address current and future medical needs.