Anti-NMNAT2 Antibody

Nicotinamide mononucleotide adenylyltransferase 2, also referred to as NMNAT2, belongs to the NMNAT family of enzymes responsible for Nicotinamide Adenine Dinucleotide (NAD⁺) biosynthesis. This family catalyzes the final step in NAD⁺ production, converting nicotinamide mononucleotide (NMN) and ATP to NAD⁺. NMNAT2 is predominantly localized in the cytoplasm and Golgi apparatus, distinguishing it from NMNAT1 (nuclear) and NMNAT3 (mitochondrial) counterparts. Structurally, NMNATs share conserved ATP-binding motifs crucial for their enzymatic functions^1-3.

In addition to its enzymatic role, NMNAT2 also functions as a chaperone, mitigating protein aggregation under proteotoxic stress. Its enzymatic and chaperone activities are recruited in a context-dependent manner, protecting against excitotoxicity and proteotoxic stress, respectively. This dual functionality highlights its significance in cellular stress responses⁵.

NMNAT2 plays a critical role in cellular energy metabolism by maintaining NAD⁺ pools, essential for redox reactions and the activity of sirtuins and PARPs, key regulators of gene expression and stress responses. NMNAT2's cytoplasmic localization facilitates its involvement in glucose metabolism and the regulation of compartmentalized NAD⁺ availability, which is crucial for processes like adipogenesis⁴. In neurons, NMNAT2 contributes to axonal protection and integrity by modulating NAD⁺-dependent repair pathways, highlighting its neuroprotective roles⁵.

NMNAT2 protein levels are tightly regulated post-transcriptionally, with a short half-life necessitating constant replenishment, and its expression is induced by glucose metabolism³. Tissue-specific expression studies reveal that NMNAT2 is highly abundant in the brain, heart, and skeletal muscle, reflecting its importance in energy-demanding tissues. At the cellular level, its expression is notable in neurons, cardiomyocytes, and other metabolically active cells^3-5.

Clinically, reduced NMNAT2 levels have been observed in neurodegenerative diseases like Alzheimer’s, where its decline precedes neurodegeneration, underscoring its potential as a therapeutic target. Dysregulated NMNAT2 activity has also been implicated in cardiac hypertrophy, demonstrating its broad relevance in disease pathophysiology^1,3,5.