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The NAD-synthesising enzyme Nmnat2 is a critical survival factor for axons in vitro and in vivo. We recently reported that loss of axonal transport vesicle association through mutations in its isoform-specific targeting and...

Animals Axons Cells Cultured Gene Deletion Mice Mice Inbred C57BL Mice Knockout Mice Transgenic Nicotinamide-Nucleotide Adenylyltransferase Structure-Activity Relationship Subcellular Fractions Wallerian degeneration

NAD metabolism regulates diverse biological processes, including ageing, circadian rhythm and axon survival. Axons depend on the activity of the central enzyme in NAD biosynthesis, nicotinamide mononucleotide adenylyltransferase...

Amidohydrolases Animals Axons Bacterial Proteins Mice Nerve Degeneration Nicotinamide Mononucleotide Nicotinamide-Nucleotide Adenylyltransferase Peripheral Nerve Injuries

We identified a homozygous missense mutation in the gene encoding NAD synthesizing enzyme NMNAT2 in two siblings with childhood onset polyneuropathy with erythromelalgia. No additional homozygotes for this rare allele, which...

Erythromelalgia NAD NMNAT2 Polyneuropathy Wallerian degeneration Erythromelalgia Female Homozygote Humans Mutation Missense Nicotinamide-Nucleotide Adenylyltransferase Pedigree Polyneuropathies Siblings Wallerian degeneration

A novel assay procedure has been developed to allow simultaneous activity discrimination in crude tissue extracts of the three known mammalian nicotinamide mononucleotide adenylyltransferase (NMNAT, EC 2.7.7.1) isozymes. These...

Animals Brain Chromatography High Pressure Liquid Liver Mice Nicotinamide-Nucleotide Adenylyltransferase

Wallerian degeneration of physically injured axons involves a well-defined molecular pathway linking loss of axonal survival factor NMNAT2 to activation of pro-degenerative protein SARM1. Manipulating the pathway through these...

axon degeneration MITOCHONDRIAL DYSFUNCTION NMNAT2 Parkinson's Disease PINK1 SARM1 Wallerian degeneration Animals Armadillo Domain Proteins Axons Cytoskeletal Proteins Drosophila Male Membrane potential Mitochondrial Mice Inbred C57BL Mitochondria Nicotinamide-Nucleotide Adenylyltransferase Wallerian degeneration

Alzheimer's Disease D. melanogaster NAD synthase NMNAT Biochemistry chaperone chemical biology phosphorylated Tau Tauopathy Animals Binding Sites Drosophila HSP90 Heat-Shock Proteins Homeostasis Humans Molecular Chaperones NAD Nicotinamide-Nucleotide Adenylyltransferase Phosphorylation Synapses tau Proteins

Axons require a constant supply of the labile axon survival factor Nmnat2 from their cell bodies to avoid spontaneous axon degeneration. Here we investigate the mechanism of fast axonal transport of Nmnat2 and its site of action...

Amino Acid Motifs Animals Axons Cell Survival Cells Cultured Exons Golgi Apparatus Half-Life Intracellular Membranes Lipoylation Mice Mice Inbred C57BL Neurons Nicotinamide-Nucleotide Adenylyltransferase Primary Cell Culture Protein Multimerization Protein Stability Protein Transport Single-Cell Analysis Time-Lapse Imaging Transport Vesicles Ubiquitination

Neurons rely heavily on axonal transport to deliver materials from the sites of synthesis to the axon terminals over distances that can be many centimetres long. KIF1A is the neuron-specific kinesin with the fastest reported...

BACE1 KIF1A Axonal Transport live-cell imaging Amyloid Precursor Protein Secretases Animals Aspartic Acid Endopeptidases Axonal Transport Cells Cultured Green Fluorescent Proteins Kinesins Luminescent Proteins Mice Inbred C57BL Microscopy Fluorescence Motor Neurons Nicotinamide-Nucleotide Adenylyltransferase Protein Transport Signal Transduction Superior Cervical Ganglion

Wallerian degeneration is delayed when sufficient levels of proteins with NMNAT activity are maintained within axons after injury. This has been proposed to form the basis of 'slow Wallerian degeneration' (Wld (S)), a...

Animals Axons Butadienes Cell Line Enzyme Stability Humans MAP Kinase Kinase 1 MAP Kinase Kinase 2 MAP Kinase Kinase 5 MAP Kinase Signaling System Nicotinamide-Nucleotide Adenylyltransferase Nitriles Phenotype Protein Kinase Inhibitors Rats Superior Cervical Ganglion Wallerian degeneration

The NAD-synthesizing enzyme NMNAT2 is critical for axon survival in primary culture and its depletion may contribute to axon degeneration in a variety of neurodegenerative disorders. Here we discuss several recent reports from...

NMNAT2 Wallerian degeneration Axon growth axon survival Axonal Transport neurodegeneration palmitoylation ubiquitin proteasome Animals Axons Gene Deletion Nerve Degeneration Neurites Nicotinamide-Nucleotide Adenylyltransferase Subcellular Fractions Wallerian degeneration

Wallerian degeneration is a widespread mechanism of programmed axon degeneration. In the three decades since the discovery of the Wallerian degeneration slow (WldS) mouse, research has generated extensive knowledge of the...

Animals Armadillo Domain Proteins Cytoskeletal Proteins Disease Models Animal Drosophila melanogaster Humans Mice Mice Transgenic NAD Nicotinamide-Nucleotide Adenylyltransferase Signal Transduction Translational Research Biomedical Wallerian degeneration

Axonal transport is critical for supplying newly synthesized proteins, organelles, mRNAs, and other cargoes from neuronal cell bodies into axons. Its impairment in many neurodegenerative conditions appears likely to contribute...

aging Axon regeneration Axonal Transport Fluorescence live imaging Mitochondrial transport Nicotinamide mononucleotide Adenylyltransferase 2 aging Animals Axonal Transport Axons Female Humans Male Mice Inbred C57BL Mice Transgenic Mitochondria Molecular Imaging Nerve Regeneration Neurodegenerative Diseases Nicotinamide-Nucleotide Adenylyltransferase Optical Imaging Peripheral Nerves Tibial Nerve

APT1 APT2 enzyme Intracellular Trafficking NMNAT2 neurodegeneration Palmitoyltransferase Protein Acylation Protein Palmitoylation zDHHC17 Acyltransferases Animals Axons Blotting Western Cell Membrane Cells Cultured HEK293 Cells Humans Lipoylation Mice Inbred C57BL Mutation Neurons Nicotinamide-Nucleotide Adenylyltransferase Palmitic Acid Propiolactone RNA Interference Reverse Transcriptase Polymerase Chain Reaction Substrate Specificity Thiolester Hydrolases

SARM1 function and nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) loss both promote axon degeneration, but their relative relationship in the process is unknown. Here, we show that NMNAT2 loss and resultant changes...

Animals Armadillo Domain Proteins Axons Cell Survival Cytoskeletal Proteins Mice Nerve Degeneration Nicotinamide-Nucleotide Adenylyltransferase

Axon degeneration is a prominent early feature of most neurodegenerative disorders and can also be induced directly by nerve injury in a process known as Wallerian degeneration. The discovery of genetic mutations that delay...

Animals Armadillo Domain Proteins Axons Cell Death Cytoskeletal Proteins Humans Intracellular Signaling Peptides and Proteins Membrane Proteins Neural Pathways Neurons Nicotinamide-Nucleotide Adenylyltransferase Wallerian degeneration

Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is an endogenous axon maintenance factor that preserves axon health by blocking Wallerian-like axon degeneration. Mice lacking NMNAT2 die at birth with severe axon...

Age Factors Animals Axons Female Male Mice Nerve Degeneration Neurogenesis Neurons Nicotinamide-Nucleotide Adenylyltransferase Primary Cell Culture