Affinage

NMNAT1

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 · UniProt Q9HAN9

Length
279 aa
Mass
31.9 kDa
Annotated
2026-06-10
98 papers in source corpus 30 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NMNAT1 is a nuclear enzyme that synthesizes NAD+ from ATP and NMN and serves as a central guardian of neuronal integrity and NAD+ homeostasis (PMID:11248244, PMID:11770485). Its identification as the active component of the WldS axon-protective fusion protein established that altered pyridine nucleotide metabolism delays axon degeneration, with enzymatic activity required for this protection (PMID:11770485, PMID:17207927, PMID:19237597). Although NMNAT1 is constitutively nuclear, its axon-protective function depends on activity localized outside the nucleus: cytoplasmic and axonally targeted NMNAT1 is sufficient to delay Wallerian degeneration and acts locally within the axon (PMID:19458223, PMID:20926655, PMID:21071441). Mechanistically, NMNAT1 protects injured axons not by boosting NAD+ synthesis but by blocking SARM1-dependent NAD+ depletion, the central degenerative trigger; loss of NMNAT1 activates the NADase SARM1, and SARM1 depletion rescues photoreceptor death in NMNAT1-deficient retinas (PMID:27735788, PMID:33107823). Independent of its catalytic activity, NMNAT1 functions as a molecular chaperone that is recruited with Hsp70 into protein aggregates and promotes clearance of misfolded proteins, including phospho-tau and mutant Huntingtin, through the ubiquitin-proteasome system and autophagy (PMID:18344983, PMID:21965302, PMID:31484760). In the nucleus, NMNAT1 couples local NAD+ production to gene regulation: it associates with the nucleomethylin/SirT1 complex to repress rRNA transcription, stimulates SirT1 deacetylase activity, and dampens p53-driven apoptosis via NAD+-dependent PARylation and deacetylation (PMID:23737528, PMID:34919052). In humans, loss-of-function mutations in NMNAT1 cause Leber congenital amaurosis, with disease alleles reducing enzymatic activity and/or destabilizing the protein (PMID:22842227, PMID:22842230, PMID:22842231, PMID:26018082); in the retina, NMNAT1 deficiency drives NAD+ decline, oxidative DNA damage, and photoreceptor apoptosis (PMID:33709122, PMID:41922335).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2001 High

    Established that NMNAT1 is the functional neuroprotective effector of the WldS protein, linking axon protection to NAD+ metabolism, and defined NMNAT1 as a nuclear NAD+-synthesizing enzyme.

    Evidence Transgenic mouse overexpression with enzyme activity assays and immunofluorescence; protein purification from human placenta with in vitro NAD+ synthesis and PARP1 inhibition assays

    PMID:11248244 PMID:11770485

    Open questions at the time
    • Nuclear localization seemed incompatible with axon protection occurring in the cytoplasm
    • Whether enzymatic activity per se was required was not yet resolved
  2. 2006 High

    Tested whether catalysis is required for protection, with conflicting answers that defined a dual-function model: enzyme activity is needed for WldS axon protection in mice, yet enzyme-dead NMNAT still rescues neurodegeneration in Drosophila.

    Evidence Site-directed active-site mutagenesis (Phe28) with neuronal axon degeneration assays in mice; forward genetic loss-of-function screen and enzyme-dead rescue in Drosophila

    PMID:17132048 PMID:17207927

    Open questions at the time
    • The molecular basis of the NAD-independent neuroprotective activity was undefined
    • Did not resolve whether the two activities act in the same or different cell compartments
  3. 2008 High

    Identified the NAD-independent activity as a chaperone function, explaining how NMNAT can protect neurons without synthesizing NAD+.

    Evidence Biochemical chaperone assays, co-localization with Hsp70 in aggregates, and proteasome pathway inhibition in cultured cells

    PMID:18344983

    Open questions at the time
    • The structural determinants of chaperone activity were not mapped
    • Direct substrate range of the chaperone function was not defined
  4. 2009 High

    Dissected the WldS protective module, showing protection requires both NMNAT1 catalysis and the N16/Ube4b VCP-binding sequence, and that cytoplasmic NMNAT1 alone suffices for axon protection.

    Evidence In vivo Drosophila and transgenic mouse axon protection assays with domain deletions, VCP-binding domain swaps, enzyme-dead mutants, and cytoplasmic-targeted NMNAT1

    PMID:19237596 PMID:19237597 PMID:19458223

    Open questions at the time
    • How VCP interaction mechanistically cooperates with NAD+ synthesis was not established
    • The endogenous compartment in which NMNAT1 acts during physiological injury was unclear
  5. 2010 High

    Demonstrated that axonal/local targeting of NMNAT1 activity is necessary and sufficient and that protection occurs locally within the axon, refining where the enzyme must act.

    Evidence Transgenic mice with axonal targeting peptide fusions and disrupted NLS, live imaging of vesicular/mitochondrial co-transport; protein transduction into severed axons via virus-like particles

    PMID:20926655 PMID:21071441

    Open questions at the time
    • The axonal vesicular/mitochondrial association mechanism was not molecularly defined
    • Protein-transduction study was a single-lab in vitro demonstration
  6. 2011 Medium

    Connected nuclear NMNAT1 to gene regulation and protein clearance, showing it stimulates SirT1 to repress rRNA transcription and promotes ubiquitin-dependent clearance of toxic phospho-tau independent of NAD synthesis.

    Evidence Co-immunoprecipitation, knockdown, rRNA transcription and SirT1 deacetylase assays; Drosophila tauopathy model with enzyme-dead NMNAT, in vivo phospho-tau Co-IP and ubiquitination assays

    PMID:21965302 PMID:23737528

    Open questions at the time
    • Single-lab Co-IP evidence without structural detail of the ternary complex
    • Whether SirT1 stimulation and tau clearance operate in the same pathway is unknown
  7. 2012 High

    Established NMNAT1 as a Mendelian disease gene, showing loss-of-function mutations cause Leber congenital amaurosis through reduced NAD+ biosynthetic activity and impaired protein folding.

    Evidence Exome sequencing of LCA patients and functional enzyme activity plus protein folding assays of mutant alleles, replicated across independent cohort papers

    PMID:22842227 PMID:22842230 PMID:22842231

    Open questions at the time
    • Why a ubiquitous enzyme causes a retina-specific disease was unexplained
    • The downstream degenerative pathway in photoreceptors was not yet defined
  8. 2012 High

    Placed NMNAT in an injury-signaling pathway by showing the E3 ligase Highwire drives its rapid post-injury degradation, identifying regulated NMNAT turnover as a control point for axon degeneration.

    Evidence Drosophila genetic epistasis with hiw loss- and gain-of-function, protein-level western blots, and in vivo axon degeneration assays

    PMID:23226106

    Open questions at the time
    • Whether a mammalian Highwire ortholog regulates NMNAT1 the same way was not tested here
    • The signal triggering Hiw-dependent NMNAT degradation was unknown
  9. 2016 High

    Redefined the protective mechanism, showing NMNAT1 prevents axon degeneration by blocking SARM1-mediated NAD+ depletion rather than by net NAD+ synthesis.

    Evidence Steady-state and metabolic flux analysis of NAD+ metabolites in mouse DRG axons with SARM1 genetic manipulation

    PMID:27735788

    Open questions at the time
    • The direct biochemical relationship between NMNAT1 and SARM1 was not structurally resolved
    • How NMNAT1 levels are coupled to SARM1 activation kinetics was not detailed
  10. 2015 Medium

    Refined the disease mechanism by showing most LCA mutants retain catalytic activity but are thermally unstable, implicating protein destabilization rather than direct catalytic loss.

    Evidence Recombinant mutant protein enzyme, heat-shock stability, secondary structure, and oligomerization assays

    PMID:26018082

    Open questions at the time
    • Single-lab biochemistry not independently replicated
    • Did not test instability in photoreceptors in vivo
  11. 2020 High

    Identified SARM1 inhibition as the essential function of NMNAT1 in photoreceptors, explaining retinal vulnerability in NMNAT1 deficiency.

    Evidence Photoreceptor-specific conditional knockout mice with genetic SARM1-depletion rescue

    PMID:33107823

    Open questions at the time
    • Whether SARM1 fully accounts for human LCA pathology was not established
    • The relative contribution of nuclear vs cytoplasmic NMNAT1 in photoreceptors was not dissected
  12. 2021 Medium

    Expanded the functional repertoire to autophagic aggregate clearance, p53/apoptosis regulation, and photoreceptor metabolic/transcriptional roles, and detailed retinal degeneration involving NAD+ decline and PARP overactivation.

    Evidence Drosophila HD and glioma models with autophagy, PARylation/deacetylation and Co-IP assays; conditional KO retinal transcriptomics/metabolomics; mouse p.Val9Met NAD+/PARP/PAR/TUNEL analyses

    PMID:31484760 PMID:33709122 PMID:34878972 PMID:34919052

    Open questions at the time
    • These roles rest largely on single-lab studies in disparate model systems
    • How nuclear NAD+ depletion mechanistically links to PARP overactivation and cell death is incompletely defined
  13. 2024 Medium

    Began defining regulation and chromatin-coupled roles of NMNAT1, showing EP300-mediated lactylation maintains nuclear activity, NMNAT1 is required for retinal lineage commitment via a NAD-PARP1 axis, and it binds active promoters to couple NAD+ production to Pol II engagement.

    Evidence Lactylation site mutagenesis with EP300 Co-IP and fractionation; CRISPR-KO iPSC retinal organoids with NAD+/PARylation readouts; CUT&Tag with RNA-seq in KO cells (preprint)

    PMID:38467179 PMID:39446354 PMID:40654636

    Open questions at the time
    • The genome-wide chromatin-binding model derives from a preprint
    • How NMNAT1 is recruited to specific promoters/enhancers is unknown
  14. 2026 Medium

    Advanced structural and cell-death mechanism understanding, providing a cryo-EM structure of inhibitor-bound NMNAT1 and showing the V9M retinal phenotype proceeds via oxidative DNA damage and caspase-9 apoptosis rescuable by antioxidant treatment.

    Evidence Cryo-EM of NMNAT1-AMI-1 with biochemical inhibition assays (preprint); V9M knock-in mice with 8-oxo-dG, γH2AX, caspase-9, TUNEL assays and NAC intervention

    PMID:41922335 PMID:41993279

    Open questions at the time
    • Cryo-EM inhibitor study is a non-peer-reviewed preprint
    • Reconciling the oxidative-DNA-damage/caspase-9 mechanism with the SARM1-dependent model remains open

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NMNAT1's distinct activities — nuclear NAD+ synthesis, SARM1 inhibition, NAD-independent chaperone/aggregate clearance, and promoter-coupled transcriptional regulation — are integrated, compartmentally partitioned, and selectively deployed in a cell-type-specific manner remains unresolved.
  • No unified structural/mechanistic model links NMNAT1's enzymatic and chaperone functions
  • The basis for retina-specific vulnerability despite ubiquitous expression is incompletely explained
  • Direct physical interaction mode with SARM1 is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0044183 protein folding chaperone 3 GO:0098772 molecular function regulator activity 3 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005730 nucleolus 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
EP300HSP70KNOP1PARP1SARM1SIRT1TP53VCP
Complex memberships
nucleomethylin/SirT1 complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 NMNAT1 (Nmnat) is the active neuroprotective component of the WldS chimeric protein (Ube4b/Nmnat fusion); the WldS protein is located predominantly in the nucleus and Nmnat enzyme activity is increased fourfold in WldS tissues, indicating axon protection is mediated through altered pyridine nucleotide metabolism. Transgenic mouse overexpression; biochemical enzyme activity assay; subcellular localization by immunofluorescence Nature neuroscience High 11770485
2001 Human NMNAT1 is a nuclear enzyme (confirmed by immunofluorescence of nuclear localization signal) that catalyzes NAD+ synthesis from ATP and NMN; recombinant NMNAT1 strongly inhibits PARP1 activity in vitro; endogenous and recombinant NMNAT1 are phosphorylated by nuclear kinases in nuclear extracts. Protein purification from human placenta; recombinant expression; immunofluorescence; in vitro PARP1 inhibition assay; [γ-32P]ATP phosphorylation assay in nuclear extracts FEBS letters High 11248244
2006 Phe28 of mouse Nmnat1 is critical for enzymatic activity; the Phe28 point mutation in WldS completely abolishes Nmnat enzyme activity and eliminates axon-protective function, confirming that Nmnat1 enzymatic activity is required for WldS-mediated axon protection. Site-directed mutagenesis; in vitro enzyme activity assay; herpes virus-mediated neuronal expression with axon degeneration morphological assay Neuroscience letters Medium 17207927
2006 In Drosophila, enzymatically inactive NMNAT protein retains significant neuroprotective effects and rescues neurodegeneration caused by loss of nmnat, demonstrating an NAD-independent requirement of NMNAT for maintaining neuronal integrity. Forward genetic screen for nmnat loss-of-function mutations in Drosophila; rescue experiments with enzyme-dead NMNAT in vivo PLoS biology High 17132048
2008 NMNAT displays chaperone function in biochemical assays and cultured cells; it shares structural similarity with known chaperones, is upregulated in the brain upon polyglutamine-expanded protein overexpression, and is recruited with Hsp70 into protein aggregates, acting through a proteasome-mediated pathway similar to Hsp70. Biochemical chaperone assays; cell culture; co-localization with Hsp70 in protein aggregates; proteasome pathway inhibition Nature High 18344983
2009 WldS-mediated suppression of Wallerian degeneration requires both Nmnat1 enzymatic activity and interaction of the N16 domain of WldS with valosin-containing protein (VCP)/TER94; enzyme-dead versions of Nmnat1 and WldS exhibit severely reduced axon-protective function in Drosophila. In vivo Drosophila axon protection assay; enzyme-dead mutant analysis; N16 domain deletion and VCP-binding domain replacement The Journal of cell biology High 19237597
2009 In mice, WldS requires both Nmnat1 enzymatic activity and the VCP-binding sequence from the N-terminal Ube4b domain for axon protection; removing the VCP-binding sequence abolishes protection, and replacing it with an ataxin-3-derived VCP-binding sequence restores it; enzyme-dead WldS cannot delay Wallerian degeneration in vivo. In vivo transgenic mouse sciatic nerve transection model; VCP-binding domain deletion and substitution mutants The Journal of cell biology High 19237596
2009 Cytoplasmic/axonally localized Nmnat1 (cytNmnat1) is sufficient to delay Wallerian degeneration in vivo in transgenic mice without any Ube4b sequences, demonstrating that Nmnat enzymatic activity outside the nucleus is required and sufficient for axon protection. Transgenic mouse generation with cytoplasmic-targeted Nmnat1; sciatic nerve transection; microscopic analysis The Journal of neuroscience High 19458223
2010 Axonal targeting of NMNAT1 activity is both necessary and sufficient for axon protection; fusing an axonal targeting peptide from APP to NMNAT1 with disrupted nuclear localization transforms it from an ineffective molecule into one more potent than WldS in transgenic mice; axonally targeted NMNAT1 localizes to vesicular structures and co-transports at least partially with mitochondria. Transgenic mouse generation; axonal targeting peptide fusion; subcellular localization by live imaging; sciatic nerve transection assay The Journal of neuroscience High 20926655
2010 Transduction of Nmnat protein directly into severed axons via virus-like particles prevents axonal degeneration post-injury, establishing that Nmnat's protective effects occur locally within the axon. Protein transduction via virus-like particles into transected axons; in vitro axon degeneration assay The Journal of biological chemistry Medium 21071441
2011 NMNAT1 interacts with the nucleolar repressor nucleomethylin and is recruited into a ternary complex containing SirT1; NMNAT1 expression stimulates the deacetylase function of SirT1; NMNAT1 is involved in repressing rRNA transcription, and knockdown enhances rRNA transcription and promotes cell death after nutrient deprivation. Co-immunoprecipitation; knockdown; rRNA transcription assay; SirT1 deacetylase activity assay The Journal of biological chemistry Medium 23737528
2012 Loss-of-function mutations in NMNAT1 (LCA9 locus) cause Leber congenital amaurosis; the disease-causing p.Val9Met mutation decreases NMNAT1 enzyme activity, establishing that reduced NAD+ biosynthetic activity of NMNAT1 underlies retinal degeneration. Exome sequencing; functional enzyme activity assay of mutant NMNAT1 protein Nature genetics High 22842227 22842230 22842231
2012 LCA-causing NMNAT1 mutations reduce enzymatic activity and affect protein folding, as assessed by functional assays of mutant alleles. Functional enzyme activity assay; protein folding assessment of LCA mutant proteins Nature genetics High 22842230
2012 The E3 ubiquitin ligase Highwire (Hiw) promotes rapid degradation of Nmnat protein in the distal axon stump after injury; increased Nmnat protein levels in hiw mutants are both required and sufficient to inhibit Wallerian degeneration, placing Nmnat downstream of Hiw in the axon degeneration pathway. Drosophila genetic epistasis; hiw loss-of-function and gain-of-function; protein level measurement by western blot; in vivo axon degeneration assay PLoS biology High 23226106
2016 NMNAT1 overexpression protects injured axons by blocking SARM1-dependent NAD+ consumption (rather than by increasing NAD+ synthesis); using steady-state and flux analysis, NMNAT1 was found to inhibit injury-induced, SARM1-mediated NAD+ depletion that is central to axon degeneration. Steady-state and metabolic flux analysis of NAD+ metabolites in mouse DRG axons; SARM1 genetic manipulation eLife High 27735788
2020 NMNAT1 loss in photoreceptors activates the NADase SARM1 (the central executioner of axon degeneration), triggering photoreceptor death; SARM1 depletion rescues photoreceptor loss in NMNAT1-deficient retinas, establishing that NMNAT1's essential function in photoreceptors is to inhibit SARM1. Conditional knockout mice; SARM1 genetic depletion rescue experiment; photoreceptor-specific conditional deletion eLife High 33107823
2015 Most LCA-associated NMNAT1 mutants have normal enzymatic activity under standard conditions, but their secondary structure is less thermally stable (they lose activity after heat shock while wild-type retains activity), suggesting protein instability rather than direct loss of catalytic activity is a mechanism underlying retinal degeneration. Recombinant protein expression; enzyme activity assay; heat shock stability assay; secondary structure analysis; oligomerization assay The Journal of biological chemistry Medium 26018082
2011 NMNAT overexpression suppresses tauopathy-induced neurodegeneration by reducing hyperphosphorylated tau oligomer levels; NMNAT interacts with phosphorylated tau in vivo and promotes ubiquitination and clearance of toxic tau species; this protective activity is independent of NAD synthesis activity, indicating direct protein-protein interaction. Drosophila tauopathy model; overexpression with enzyme-dead NMNAT; co-immunoprecipitation with phospho-tau in vivo; ubiquitination assay Human molecular genetics Medium 21965302
2021 NMNAT promotes autophagic clearance of mutant Huntingtin aggregates in Drosophila HD models; it reduces the amyloid-like adhesive property of Htt aggregates and inhibits their clustering with mitochondria and synaptic proteins; partial loss of endogenous Nmnat exacerbates mutant Htt-induced neurodegeneration. Drosophila HD model; Nmnat overexpression and partial loss-of-function; autophagy assay; thioflavin S staining for amyloid-like aggregates; mitochondrial clustering analysis Proceedings of the National Academy of Sciences Medium 31484760
2021 NMNAT interferes with the DNA damage-p53-caspase-3 apoptosis pathway by enhancing NAD+-dependent post-translational modifications: PARylation and deacetylation of p53, which reduce p53 pro-apoptotic activity; NMNAT forms a protein complex with p53 and NAD+-dependent PTM enzymes. Drosophila glial neoplasia model and human glioma cells; co-immunoprecipitation; p53 PARylation and deacetylation assays; enzyme-dead NMNAT controls eLife Medium 34919052
2021 NMNAT1 knockout in the developing murine retina causes disruptions to central carbon metabolism, purine nucleotide synthesis, and amino acid pathways; transcriptomic analysis reveals dysregulation of photoreceptor and synapse-specific genes prior to detectable morphological or metabolic changes, suggesting a role in gene regulation during photoreceptor terminal differentiation. Conditional knockout mice; transcriptomics (RNA-seq); metabolomics; immunostaining eLife Medium 34878972
2021 NMNAT1 loss in photoreceptors leads to a retina-specific decrease in NAD+ and overproduction of poly(ADP-ribose) (PAR) by PARP in photoreceptors, while nuclear sirtuin deacetylation activity is not altered; photoreceptors ultimately die by apoptosis, with aspects of the parthanatos pathway. Mouse model (p.Val9Met); LC-MS/MS quantification of NAD+; PARP activity assay; PAR immunostaining; TUNEL staining Human molecular genetics Medium 33709122
2024 NMNAT1 is lactylated at Lys128 by the lactyltransferase EP300; lactylation of NMNAT1 enhances its nuclear localization and maintains its enzymatic activity, thereby supporting the nuclear NAD+ salvage pathway in pancreatic cancer cells under glucose deprivation. Multi-omics analysis; site-directed mutagenesis at K128; RNA interference; co-immunoprecipitation with EP300; subcellular fractionation; enzyme activity assay Cancer letters Medium 38467179
2024 NMNAT1 is essential for human iPSC differentiation to the retinal lineage; NMNAT1-KO organoids fail to induce RAX and form retinal primordial structures; NMNAT1-KO leads to decreased NAD+ levels and reduced PARylation of PARP1, identifying a NMNAT1-NAD-PARP1 axis in retinal fate commitment. CRISPR/Cas9 NMNAT1-KO human iPSC retinal organoids; transcriptomic analysis; mass spectrometry of PARylated proteins; intracellular NAD measurement Investigative ophthalmology & visual science Medium 39446354
2001 Human NMNAT1 was crystallized in the presence of NAD+; crystals diffract to 3.0 Å resolution, and packing considerations suggest a hexameric assembly in the asymmetric unit, consistent with archaeal NMNAT hexamers. Protein crystallization; preliminary X-ray diffraction analysis Acta crystallographica Section D Low 11752792
2025 NMNAT1 binds to promoters and enhancers of actively transcribed genes genome-wide; NMNAT1 knockout reduces RNA Polymerase II occupancy at downregulated genes, positioning NMNAT1 as coupling localized NAD+ production to gene-specific transcriptional activation through Pol II engagement. CUT&Tag (genome-wide NMNAT1 binding); RNA-seq; NMNAT1 knockout cells; multi-omics integration bioRxivpreprint Medium 40654636
2026 AMI-1 (a known PRMT1 inhibitor) also inhibits NMNAT1; cryo-EM structure of NMNAT1 bound to AMI-1 reveals its mechanism of inhibition at atomic resolution. Cryo-EM structure determination; biochemical inhibition assay; NAD+ level measurement in NMNAT1-dependent cancer cells bioRxivpreprint Medium 41993279
2025 KNOP1 directly interacts with NMNAT1 to maintain intracellular NAD+ homeostasis; this interaction inhibits FoxO1 phosphorylation and promotes its nuclear retention, facilitating GPX4 transcription and suppressing ferroptosis in breast cancer cells; NMNAT1 knockdown disrupts this axis by inducing FoxO1 nuclear export and GPX4 downregulation. Co-immunoprecipitation; ChIP; NAD+ quantification; RNA interference; rescue experiments with Ferrostatin-1 and NMNAT1 overexpression Cellular signalling Medium 40784594
2026 Reduced NMNAT1 function (p.V9M mutation) leads to accumulation of oxidative DNA adduct 8-oxo-dG and DNA double-strand breaks in photoreceptors, followed by caspase-9-mediated apoptosis; necroptosis and parthanatos pathways are not significantly activated; treatment with antioxidant NAC reduces oxidative DNA damage and preserves photoreceptor structure and function. Nmnat1 V9M/V9M knock-in mice; 8-oxo-dG immunostaining; γH2AX staining; caspase-9 activation assay; TUNEL; NAC treatment; OCT and ERG Cell death & disease Medium 41922335

Source papers

Stage 0 corpus · 98 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nature neuroscience 515 11770485
2010 Wallerian degeneration, wld(s), and nmnat. Annual review of neuroscience 384 20345246
2008 NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration. Nature 169 18344983
2012 NMNAT1 mutations cause Leber congenital amaurosis. Nature genetics 163 22842227
2016 NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion. eLife 162 27735788
2012 Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration. Nature genetics 162 22842230
2012 The Highwire ubiquitin ligase promotes axonal degeneration by tuning levels of Nmnat protein. PLoS biology 160 23226106
2006 Drosophila NMNAT maintains neural integrity independent of its NAD synthesis activity. PLoS biology 135 17132048
2008 Nmnat delays axonal degeneration caused by mitochondrial and oxidative stress. The Journal of neuroscience : the official journal of the Society for Neuroscience 128 18463239
2009 Transgenic mice expressing the Nmnat1 protein manifest robust delay in axonal degeneration in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 127 19458223
2009 The NMN/NaMN adenylyltransferase (NMNAT) protein family. Frontiers in bioscience (Landmark edition) 120 19273075
2012 A novel Drosophila model of nerve injury reveals an essential role of Nmnat in maintaining axonal integrity. Current biology : CB 117 22425156
2009 Wld S requires Nmnat1 enzymatic activity and N16-VCP interactions to suppress Wallerian degeneration. The Journal of cell biology 117 19237597
2001 Characterization of recombinant human nicotinamide mononucleotide adenylyl transferase (NMNAT), a nuclear enzyme essential for NAD synthesis. FEBS letters 117 11248244
2006 NAD(+) and axon degeneration revisited: Nmnat1 cannot substitute for Wld(S) to delay Wallerian degeneration. Cell death and differentiation 116 16645633
2012 Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis. Nature genetics 108 22842231
2010 Targeting NMNAT1 to axons and synapses transforms its neuroprotective potency in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 102 20926655
2009 Wld S protein requires Nmnat activity and a short N-terminal sequence to protect axons in mice. The Journal of cell biology 98 19237596
2002 Age-dependent synapse withdrawal at axotomised neuromuscular junctions in Wld(s) mutant and Ube4b/Nmnat transgenic mice. The Journal of physiology 84 12231635
2011 NMNAT suppresses tau-induced neurodegeneration by promoting clearance of hyperphosphorylated tau oligomers in a Drosophila model of tauopathy. Human molecular genetics 82 21965302
2011 NMNAT expression and its relation to NAD metabolism. Current medicinal chemistry 75 21517776
2024 Lactate enhances NMNAT1 lactylation to sustain nuclear NAD+ salvage pathway and promote survival of pancreatic adenocarcinoma cells under glucose-deprived conditions. Cancer letters 73 38467179
2013 Mislocalization of neuronal mitochondria reveals regulation of Wallerian degeneration and NMNAT/WLD(S)-mediated axon protection independent of axonal mitochondria. Human molecular genetics 66 23314018
2011 Reducing expression of NAD+ synthesizing enzyme NMNAT1 does not affect the rate of Wallerian degeneration. The FEBS journal 65 21615689
2020 SARM1 depletion rescues NMNAT1-dependent photoreceptor cell death and retinal degeneration. eLife 63 33107823
2013 Protection of mouse retinal ganglion cell axons and soma from glaucomatous and ischemic injury by cytoplasmic overexpression of Nmnat1. Investigative ophthalmology & visual science 58 23211826
2010 Axonal degeneration is blocked by nicotinamide mononucleotide adenylyltransferase (Nmnat) protein transduction into transected axons. The Journal of biological chemistry 57 21071441
2003 Identification of a locus (LCA9) for Leber's congenital amaurosis on chromosome 1p36. European journal of human genetics : EJHG 45 12734549
2011 Nmnat exerts neuroprotective effects in dendrites and axons. Molecular and cellular neurosciences 43 21596138
2016 Mouse Models of NMNAT1-Leber Congenital Amaurosis (LCA9) Recapitulate Key Features of the Human Disease. The American journal of pathology 38 27207593
2015 Alternative splicing of Drosophila Nmnat functions as a switch to enhance neuroprotection under stress. Nature communications 37 26616331
2015 Characterization of Leber Congenital Amaurosis-associated NMNAT1 Mutants. The Journal of biological chemistry 36 26018082
2016 Mitochondria and Caspases Tune Nmnat-Mediated Stabilization to Promote Axon Regeneration. PLoS genetics 35 27923046
2013 The NAD+ synthesis enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT1) regulates ribosomal RNA transcription. The Journal of biological chemistry 35 23737528
2011 NMN/NaMN adenylyltransferase (NMNAT) and NAD kinase (NADK) inhibitors: chemistry and potential therapeutic applications. Current medicinal chemistry 35 21517775
2014 The NAD+ synthesizing enzyme nicotinamide mononucleotide adenylyltransferase 2 (NMNAT-2) is a p53 downstream target. Cell cycle (Georgetown, Tex.) 34 24552824
2015 Hidden Genetic Variation in LCA9-Associated Congenital Blindness Explained by 5'UTR Mutations and Copy-Number Variations of NMNAT1. Human mutation 30 26316326
2006 Identification of a critical site in Wld(s): essential for Nmnat enzyme activity and axon-protective function. Neuroscience letters 30 17207927
2019 Nmnat restores neuronal integrity by neutralizing mutant Huntingtin aggregate-induced progressive toxicity. Proceedings of the National Academy of Sciences of the United States of America 29 31484760
2012 Simultaneous single-sample determination of NMNAT isozyme activities in mouse tissues. PloS one 29 23300904
2014 YCL047C/POF1 is a novel nicotinamide mononucleotide adenylyltransferase (NMNAT) in Saccharomyces cerevisiae. The Journal of biological chemistry 25 24759102
2014 Nonpenetrance of the most frequent autosomal recessive leber congenital amaurosis mutation in NMNAT1. JAMA ophthalmology 25 24830548
2014 Novel compound heterozygous NMNAT1 variants associated with Leber congenital amaurosis. Molecular vision 23 24940029
2012 WldS but not Nmnat1 protects dopaminergic neurites from MPP+ neurotoxicity. Molecular neurodegeneration 22 22315973
2021 NMNAT promotes glioma growth through regulating post-translational modifications of P53 to inhibit apoptosis. eLife 21 34919052
2006 Protection of vincristine-induced neuropathy by WldS expression and the independence of the activity of Nmnat1. Neuroscience letters 21 17113230
2021 Nuclear NAD+-biosynthetic enzyme NMNAT1 facilitates development and early survival of retinal neurons. eLife 20 34878972
2018 NMNAT1 E257K variant, associated with Leber Congenital Amaurosis (LCA9), causes a mild retinal degeneration phenotype. Experimental eye research 20 29674119
2017 NMNAT1 variants cause cone and cone-rod dystrophy. European journal of human genetics : EJHG 20 29184169
2016 Nmnat1 protects neuronal function without altering phospho-tau pathology in a mouse model of tauopathy. Annals of clinical and translational neurology 19 27547771
2021 Mutant Nmnat1 leads to a retina-specific decrease of NAD+ accompanied by increased poly(ADP-ribose) in a mouse model of NMNAT1-associated retinal degeneration. Human molecular genetics 18 33709122
2021 Activation of cardiac Nmnat/NAD+/SIR2 pathways mediates endurance exercise resistance to lipotoxic cardiomyopathy in aging Drosophila. The Journal of experimental biology 18 34495320
2020 An Alu-mediated duplication in NMNAT1, involved in NAD biosynthesis, causes a novel syndrome, SHILCA, affecting multiple tissues and organs. Human molecular genetics 18 32533184
2017 NAD-biosynthetic enzyme NMNAT1 reduces early behavioral impairment in the htau mouse model of tauopathy. Behavioural brain research 18 29175372
2012 The role of autophagy in Nmnat-mediated protection against hypoxia-induced dendrite degeneration. Molecular and cellular neurosciences 18 23159780
2012 Molecular chaperones protect against JNK- and Nmnat-regulated axon degeneration in Drosophila. Journal of cell science 18 23264732
2020 Gene Therapy Preserves Retinal Structure and Function in a Mouse Model of NMNAT1-Associated Retinal Degeneration. Molecular therapy. Methods & clinical development 17 32775493
2018 Overexpression of Nmnat improves the adaption of health span in aging Drosophila. Experimental gerontology 16 29727704
2014 Axonal transport plays a crucial role in mediating the axon-protective effects of NmNAT. Neurobiology of disease 16 24787896
2016 Nmnat 1: a Security Guard of Retinal Ganglion Cells (RGCs) in Response to High Glucose Stress. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 15 27184051
2017 Genome-wide linkage and sequence analysis challenge CCDC66 as a human retinal dystrophy candidate gene and support a distinct NMNAT1-related fundus phenotype. Clinical genetics 12 28369829
2015 A novel missense NMNAT1 mutation identified in a consanguineous family with Leber congenital amaurosis by targeted next generation sequencing. Gene 12 25988908
2022 Human Nmnat1 Promotes Autophagic Clearance of Amyloid Plaques in a Drosophila Model of Alzheimer's Disease. Frontiers in aging neuroscience 11 35401143
2021 A NOVEL CASE SERIES OF NMNAT1-ASSOCIATED EARLY-ONSET RETINAL DYSTROPHY: EXTENDING THE PHENOTYPIC SPECTRUM. Retinal cases & brief reports 11 30004997
2020 Overexpression of nicotinamide mononucleotide adenylyltransferase (nmnat) increases the growth rate, Ca2+ concentration and cellulase production in Ganoderma lucidum. Applied microbiology and biotechnology 11 32632475
2019 Why is NMNAT Protective against Neuronal Cell Death and Axon Degeneration, but Inhibitory of Axon Regeneration? Cells 11 30901919
2019 Development of a Bioluminescent High-Throughput Screening Assay for Nicotinamide Mononucleotide Adenylyltransferase (NMNAT). SLAS discovery : advancing life sciences R & D 10 31583955
2015 Clinical and genetic findings in a family with NMNAT1-associated Leber congenital amaurosis: case report and review of the literature. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 10 26464178
2020 Effect of NMDAR-NMNAT1/2 pathway on neuronal cell damage and cognitive impairment of sevoflurane-induced aged rats. Neurological research 8 31941414
2024 Nuclear Nicotinamide Adenine Dinucleotide Deficiency by Nmnat1 Deletion Impaired Hepatic Insulin Signaling, Mitochondrial Function, and Hepatokine Expression in Mice Fed a High-Fat Diet. Laboratory investigation; a journal of technical methods and pathology 7 38237740
2023 Expression of NMNAT1 in the photoreceptors is sufficient to prevent NMNAT1-associated retinal degeneration. Molecular therapy. Methods & clinical development 7 37214313
2022 Loss of hepatic Nmnat1 has no impact on diet-induced fatty liver disease. Biochemical and biophysical research communications 7 36332487
2021 Nmnat1 Modulates Mitochondrial Oxidative Stress by Inhibiting Caspase-3 Signaling in Alzheimer's Disease. Journal of molecular neuroscience : MN 7 33447901
2023 NMNAT1 and hereditary spastic paraplegia (HSP): expanding the phenotypic spectrum of NMNAT1 variants. Neuromuscular disorders : NMD 6 36871412
2021 New Insights on the Genetic Basis Underlying SHILCA Syndrome: Characterization of the NMNAT1 Pathological Alterations Due to Compound Heterozygous Mutations and Identification of a Novel Alternative Isoform. International journal of molecular sciences 6 33668384
2021 NMNAT1 Is a Survival Factor in Actinomycin D-Induced Osteosarcoma Cell Death. International journal of molecular sciences 6 34445574
2019 NMNAT Proteins that Limit Wallerian Degeneration Also Regulate Critical Period Plasticity in the Visual Cortex. eNeuro 6 30671537
2023 Adipocyte NMNAT1 expression is essential for nuclear NAD+ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism. Biochemical and biophysical research communications 5 37421924
2025 PPDPF preserves integrity of proximal tubule by modulating NMNAT activity in chronic kidney diseases. Science advances 4 40106551
2025 Hepatic NMNAT1 is required to defend against alcohol-associated fatty liver disease. Science advances 4 40577472
2024 NMNAT1 Is Essential for Human iPS Cell Differentiation to the Retinal Lineage. Investigative ophthalmology & visual science 4 39446354
2019 MicroRNA miR-1002 Enhances NMNAT-Mediated Stress Response by Modulating Alternative Splicing. iScience 4 31522116
2011 Nicotinamide mononucleotide adenylyltransferase 1 gene NMNAT1 regulates neuronal dendrite and axon morphogenesis in vitro. Chinese medical journal 4 22088538
2024 Nmnat1 Deficiency Causes Mitoribosome Excess in Diabetic Nephropathy Mediated by Transcriptional Repressor HIC1. International journal of molecular sciences 3 38928090
2024 Identification and characterization of NMNAT1 gene mutations in an Iranian patient with Leber congenital amaurosis 9. Clinical case reports 3 39445201
2023 Deletion of Nmnat1 in Skeletal Muscle Leads to the Reduction of NAD+ Levels but Has No Impact on Skeletal Muscle Morphology and Fiber Types. Journal of nutritional science and vitaminology 3 37394423
2018 WITHDRAWN: Regular exercise protects aging Drosophila from high-fat-diet-induced locomotor impairment, cardiac dysfunction, lifespan shortening, and Nmnat and dSir2 expression decline. Experimental gerontology 3 29355704
2001 Crystallization and preliminary X-ray analysis of human nicotinamide mononucleotide adenylyltransferase (NMNAT). Acta crystallographica. Section D, Biological crystallography 3 11752792
2015 Nmnat1-Rbp7 Is a Conserved Fusion-Protein That Combines NAD+ Catalysis of Nmnat1 with Subcellular Localization of Rbp7. PloS one 2 26618989
2025 KNOP1 interacts with NMNAT1 to govern ferroptosis and tumor growth in breast cancer via regulating FoxO1-dependent GPX4 transcription. Cellular signalling 1 40784594
2026 NMNAT1 Activates Autophagy to Delay D-Galactose-Induced Aging in Cochlear Hair Cells. Aging cell 0 41521645
2026 The NAD salvage pathway enzyme NMNAT-C sustains dark-phase NAD+ homeostasis in cyanobacteria. Plant physiology 0 41838801
2026 Oxidative DNA damage drives apoptotic photoreceptor loss in NMNAT1-associated inherited retinal degeneration: a therapeutic opportunity. Cell death & disease 0 41922335
2026 Structural and biochemical characterization of a novel inhibitor of NMNAT1, the gatekeeper of nuclear NAD+ biosynthesis. bioRxiv : the preprint server for biology 0 41993279
2026 Role of NMDAR-NMNAT in sevoflurane exposure-induced learning memory deficits. Brain & development 0 42081862
2025 Circ-NMNAT1 Drives Tumor Progression in Bladder Cancer by Modulating the miR-370-3p/ATXN2L Axis. Applied biochemistry and biotechnology 0 39820928
2025 Oxidative DNA Damage Drives Apoptotic Photoreceptor Loss in NMNAT1 -Associated Inherited Retinal Degeneration: A Therapeutic Opportunity. bioRxiv : the preprint server for biology 0 40501637
2025 NMNAT1 Binding at Promoters and Enhancers Couples NAD + Synthesis to RNA Polymerase II Engagement. bioRxiv : the preprint server for biology 0 40654636

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