NMNAT1driven

NMNAT1driven refers to biological processes and phenotypes predominantly governed by the activity of NMNAT1, the nuclear nicotinamide mononucleotide adenylyltransferase responsible for generating NAD+ within the nucleus. The term underscores processes that depend on nuclear NAD+ pools for the function of NAD+-dependent enzymes and for maintenance of genomic integrity.

NMNAT1 catalyzes the conversion of nicotinamide mononucleotide and ATP to NAD+ and pyrophosphate. Located mainly in the nucleus, NMNAT1 helps sustain nuclear NAD+ levels that support enzymes such as PARP1 and SIRT1, which regulate DNA repair, chromatin remodeling, transcription, and stress responses. NMNAT1 operates alongside cytosolic and mitochondrial NMNATs, contributing to compartmentalized NAD+ homeostasis.

Biological roles frequently described as NMNAT1driven include maintenance of genome stability, effective DNA damage response, and regulation of transcription programs that depend on NAD+-dependent deacetylation or ADP-ribosylation. In neurons, NMNAT1 has been linked to axonal protection and to processes relevant for retinal cells, where NMNAT1 activity influences cell survival under metabolic stress.

Clinically, pathogenic variants in NMNAT1 cause Leber congenital amaurosis type 9 (LCA9), a severe early-onset inherited retinal dystrophy. This illustrates how NMNAT1driven NAD+ metabolism supports retinal development and function. Research into NMNAT1-driven pathways informs potential therapeutic strategies, including approaches to bolster nuclear NAD+ levels to support DNA repair and cell viability in disease contexts.