Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2)

Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is a cytoplasmic enzyme (mainly associated with the Golgi apparatus) highly enriched in neurons, where it catalyzes a key step of NAD+ biosynthesis by transferring an adenylyl group from ATP to NMN. NMNAT2 maintains neuronal NAD+ pools critical for axon survival and protection against neurodegenerative stimuli. Reduction of NMNAT2 expression is linked to diseases such as Alzheimer’s and glaucoma due to impaired NAD+ homeostasis and increased vulnerability to axon degeneration. Pharmacological activation—using agents like epigallocatechin gallate (EGCG)—demonstrates the neuroprotective potential of targeting NMNAT2. Loss of NMNAT2 leads to embryonic lethality and rapid axonal degeneration (Wallerian degeneration); conversely, its enhancement can counteract neurodegeneration via pathways including AMPK activation and upregulation of neuroprotective proteins (e.g., ADAM10).

Other names

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2C1orf15KIAA0479NMN/NaMN adenylyltransferase 2NMN adenylyltransferase 2NaMN adenylyltransferase 2PNAT2Nicotinamide mononucleotide adenylyltransferase 2Nicotinate-nucleotide adenylyltransferase 2pyridine nucleotide adenylyltransferase 2

Activation of NMNAT2 increases NAD+ biosynthesis, which protects neurons and axons from degeneration and enhances metabolic resilience. Allosteric binding by small molecules enhances NMNAT2 activity and NAD+ synthesis