Nicotinamide Nucleotide Adenylyltransferase 1 Proteins (NMNAT1)

Human Nicotinamide Nucleotide Adenylyltransferase 1 (NMNAT1) interaction partners

1. Rare homozygous variant c.[271G > A] p.(Glu91Lys) and compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys) were identified in two cases of cone-rod dystrophy, respectively.

2. Results associate a distinct retinal dystrophy phenotype with nicotinamide-nucleotide adenylyltransferase 1 protein (NMNAT1) mutation and suggest coiled-coil domain containing 66 (CCDC66) should not be considered a retinal dystrophy candidate gene.

3. Hidden Genetic Variation in LCA9-Associated Congenital Blindness Explained by 5'UTR Mutations and Copy-Number Variations of NMNAT1.

4. We confirmed a diagnosis of NMNAT1-associated Leber congenital amaurosis in two siblings through identification of the mutation (c.25G>A [p. Val9Met]) in a homozygous state.

5. NMNAT1, which encodes the nicotinamide mononucleotide adenylyltransferase 1, has been recently identified to be one of the LCA-causing genes. Our results expanded the spectrum of mutations in NMNAT1

6. To study how mutations affect NMNAT1 function and ultimately lead to a retinal degeneration phenotype, we performed detailed analysis of Leber congenital amaurosis 9-associated NMNAT1 mutants.

7. theNMNAT1 p.Glu257Lys variant is a hypomorphic variant that almost without exception causes leber congenital amaurosis (LCA) in combination with more severe NMNAT1 variants.

8. The aim of this study was to determine the occurrence and frequency of NMNAT1 mutations and associated phenotypes in different types of inherited retinal dystrophies.

9. Data found pathogenic DNA variants in the genes RP1, USH2A, CNGB3, NMNAT1, CHM, and ABCA4, responsible for retinitis pigmentosa, Usher syndrome, achromatopsia, Leber congenital amaurosis, choroideremia, or recessive Stargardt/cone-rod dystrophy cases.

10. NMNAT1 deletion in tumors may contribute to transformation by increasing ribosomal RNA synthesis.

11. mutations in nicotinamide nucleotide adenylyltransferase 1(NMNAT1) cause Leber congenital amaurosis

12. Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy.

13. A new disease mechanism underlying Leber congential amaurosis and the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder.

14. Our studies link the enzymatic activities of NMNAT-1 and PARP-1 to the regulation of a set of common target genes through functional interactions at target gene promoters.

15. Study investigated the importance of NMNAT2's central domain, which are postulated to be dispensable for catalytic activity, instead representing an isozyme-specific control domain within the overall architecture of NMNAT2.

16. nicotinamide mononucleotide adenylyltransferase (Nmnat) protein transduction into transected axons blocks axonal degeneration

17. Neuronal expression of exogenous Nmnat1 protein localized to the cytosol is essential and sufficient to delay Wallerian degeneration; cytosolic Nmnat1 showed greatly enhanced axon protection compared with native (nuclear) Nmnat1.

18. Axonal targeting of transgenic NMNAT activity is both necessary and sufficient to delay Wallerian degeneration; promoting axonal and synaptic delivery greatly enhances NMNAT1 effectiveness.

19. Red blood cells represent the first human cell type with a remarkable predominance of NMNAT3 over NMNAT1; NMNAT2 is absent.

20. analysis of isoform-specific targeting and interaction domains in human nicotinamide mononucleotide adenylyltransferases

Mouse (Murine) Nicotinamide Nucleotide Adenylyltransferase 1 (NMNAT1) interaction partners

1. We propose that the E257K allele is a weak hypomorphic allele that has significantly reduced penetrance in the homozygous state. In contrast, compound heterozygous Nmnat1(E257K/-) mice exhibit photoreceptor defects which are exacerbated upon exposure to light.

2. that increasing NMNAT1 levels can slow the progression of symptoms and neuropathological features of tauopathy

3. Using steady-state and flux analysis of NAD(+) metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD(+) synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD(+) consumption that is central to axon degeneration.

4. Mouse-non nuclear-nicotinamide mononucleotide adenylyltransferase type 1 maintains mitochondrial nicotinamide levels and thereby supports mitochondrial unfolded protein response function and mitochondrial proteostasis in injured neurons.

5. NMNAT1 overexpression enhanced AMPK activity in oxygen-glucose deprivation treated cortical neurons

6. An increased level of Nmnat protein in hiw mutants is both required and sufficient to inhibit axonal degeneration.

7. Overexpression of Nmnat1 in the cytoplasm and axons of RGCs robustly protected against both ischemic and glaucomatous loss of RGC axonal integrity, as well as loss of RGC soma.

8. Findings reveal a novel role for NMNAT1 in the morphogenesis of developing cortical neurons, which indicate that the loss of function of NMNAT1 may contribute to different neurodegenerative disorders in central nervous system.

9. Nicotinamide mononucleotide adenylyl transferase 1 protects against acute neurodegeneration in developing CNS by inhibiting excitotoxic-necrotic cell death.

10. NMNAT1 is indispensable for the normal development of the embryo. Decreased NMNAT1 activity in heterozygous null mice does not affect the rate of Wallerian degeneration, suggesting that endogenous NMNAT1 does not have a primary role in axon maintenance.

11. nicotinamide mononucleotide adenylyltransferase (Nmnat) protein transduction into transected axons blocks axonal degeneration

12. Through NAMPT activity, visfatin contributes to vascular inflammation, causing atherothrombotic diseases linked to metabolic disorders.

13. demonstrated that increased Nmnat activity is responsible for the axon-sparing activity of the Wlds protein; also demonstrated that SIRT1 is the downstream effector of increased Nmnat activity that leads to

14. Nmnat1 is significantly weaker than Wld(S) at protecting axons against traumatic or toxic injury in vitro, and has no detectable effect in vivo

15. Nmnat1 can protect severed axons from autodestruction but at levels significantly lower than Wld(S), and enzyme-dead versions of Nmnat1 and Wld(S) exhibit severely reduced axon-protective function.

16. results suggest that axonal protection by NMNAT expression in neurons is provided by modifying mitochondrial function

17. This study provided the evidence that Nmnat1 protein manifest robust delay in axonal degeneration.