Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that in humans is encoded by the ''NMNAT2''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. This gene product belongs to the

nicotinamide-nucleotide adenylyltransferase In enzymology, nicotinamide-nucleotide adenylyltransferase (NMNAT) () are enzymes that catalyzes the chemical reaction :ATP + nicotinamide mononucleotide \rightleftharpoons diphosphate + NAD+ Thus, the two substrates of this enzyme are ATP an ...

(NMNAT) enzyme family, members of which catalyze an essential step in the nicotinamide adenine dinucleotide (NAD+ (NADP)) biosynthetic pathway. NMNAT2 is cytoplasmic (associated with the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...

), and is predominantly expressed in the brain. Two transcript variants encoding different isoforms have been found for this gene. Loss of NMNAT2 initiates

Wallerian degeneration Wallerian degeneration is an active process of degeneration that results when a nerve fiber is cut or crushed and the part of the axon distal to the injury (i.e. farther from the neuron's cell body) degenerates. A related process of dying back o ...

. By contrast, NMNAT2 enhancement opposes the actions of

SARM1 Sterile alpha and TIR motif containing 1 Is an enzyme that in humans is encoded by the ''SARM1'' gene. It is the most evolutionarily conserved member of the Toll/Interleukin receptor-1 (TIR) family. SARM1's TIR domain has intrinsic NADase enzym ...

which would lead to axon degeneration, but this effect is not due to preventing SARM1 depletion of NAD+. Mice lacking NMNAT2 die before birth, but are completely rescued by SARM1 deletion. Activation of NMNAT2 by

Sirtuin 3 NAD-dependent deacetylase sirtuin-3, mitochondrial also known as SIRT3 is a protein that in humans is encoded by the ''SIRT3'' gene irtuin (silent mating type information regulation 2 homolog) 3 (S. cerevisiae) SIRT3 is member of the mammalian sir ...

(SIRT3) may be a means of inhibiting axon degeneration and dysfunction. The

catechin Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids. The name of the catechin chemical family derives from ''catechu'', which is the tannic ...

epigallocatechin gallate Epigallocatechin gallate (EGCG), also known as epigallocatechin-3-gallate, is the ester of epigallocatechin and gallic acid, and is a type of catechin. EGCG – the most abundant catechin in tea – is a polyphenol under basic research for its ...

(EGCG) found in

tea Tea is an aromatic beverage prepared by pouring hot or boiling water over cured or fresh leaves of ''Camellia sinensis'', an evergreen shrub native to East Asia which probably originated in the borderlands of southwestern China and north ...

can activate NMNAT2 by more than 100%.

References

Further reading