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.