NAD+ (Nasal)

Unlike a classic ligand-receptor peptide, NAD+ functions chiefly as an enzymatic cofactor rather than acting on a single surface receptor. Its primary targets are understood to be intracellular enzymes that consume or recycle it, including sirtuins, PARPs, and the CD38/CD157 ecto-enzymes, while cell-surface purinergic (P2) receptors may respond to extracellular NAD+ and its metabolites. Intranasal delivery is understood to favor uptake along the nasal mucosa and olfactory pathway.

NAD+ availability is understood to activate NAD+-dependent sirtuin deacylases (notably SIRT1 and SIRT3), which are linked to deacetylation of transcriptional regulators such as PGC-1alpha and FOXO. Downstream effects reach mitochondrial biogenesis signaling, the AMPK energy-sensing axis, and DNA-repair enzymes (PARPs) that draw on the NAD+ pool. These pathways are connected to cellular stress resilience and metabolic homeostasis.

Because the intranasal route is understood partly to offer access toward the central nervous system, NAD+ is considered for its potential influence on neuronal energy metabolism and redox status. NAD+ precursors are associated with support of mitochondrial function in neural tissue and with pathways relevant to neuronal maintenance, though direct receptor-mediated neural signaling is not the primary described mechanism. This area remains preliminary.

Systemically, NAD+ is central to redox reactions (the NAD+/NADH couple) that drive glycolysis, the citric acid cycle, and oxidative phosphorylation, linking it to whole-body energy metabolism. NAD+-consuming enzymes such as CD38 and the sirtuins are associated with immune signaling, circadian regulation, and metabolic flexibility. Maintaining the NAD+ pool is understood to relate to cellular aging markers and adaptive stress responses.