Ask about this productRelated genes to: NMNAT1 Blocking Peptide
- Gene:
- NMNAT1 NIH gene
- Name:
- nicotinamide nucleotide adenylyltransferase 1
- Previous symbol:
- LCA9
- Synonyms:
- NMNAT, PNAT1
- Chromosome:
- 1p36.22
- Locus Type:
- gene with protein product
- Date approved:
- 2002-02-19
- Date modifiied:
- 2014-11-19
Related products to: NMNAT1 Blocking Peptide
Related articles to: NMNAT1 Blocking Peptide
- Hereditary spastic paraplegia (HSP) refers to a heterogeneous group of genetic disorders with more than 90 causative genes. Clinically, HSP is classified into pure and complicated forms. Pure forms are characterized primarily by lower-limb spasticity and weakness, whereas complicated forms include additional neurological or non-neurological symptoms alongside spasticity and weakness. We aimed to characterize the clinical and genetic landscapes of HSP in an Iranian cohort. Whole-exome sequencing (WES) was performed on 103 unrelated clinically suspected HSP probands. Multiple ligation-dependent probe amplification (MLPA) was performed to validate identified copy number variants (CNVs) in two probands. - Source: PubMed
Publication date: 2026/05/12
Davarzani AtefehRavanbod MoezGhasemi AidaMohammadi MahsaRohani MohammadNafissi ShahriarJamali PaymanNajmabadi HosseinFatehi FarzadAlavi ShahryarFiroozfar ZahraZemorshidi FaribaHabibi-Kavashkohie Mohammad RezaAlavi Afagh - This study investigated the roles of CREB and NMNATs in sevoflurane-induced cognitive deficits and synaptic alterations in developing hippocampal neurons. - Source: PubMed
Publication date: 2026/05/03
Hu NanJi WeiweiDou JingChen Xi - Mitochondrial dysfunction plays a critical role in glaucomatous trabecular meshwork (TM) degeneration, whereas increasing intracellular nicotinamide adenine dinucleotide (NAD) levels can restore mitochondrial homeostasis, offering therapeutic benefits for glaucoma. We propose that intracellular NAD can be boosted by promoting NAD biosynthesis through the co-delivery of nicotinamide (NAM), an NAD precursor, and the gene encoding nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1), the rate-limiting enzyme for NAD biosynthesis that consumes NAM. To achieve high gene transfection efficiency, the Nmnat1 gene was encapsulated in a multifunctional lipid nanoparticle (Nmnat1-LNPs). The combination of Nmnat1-LNPs and NAM synergistically reversed mitochondrial dysfunction in primary human trabecular meshwork cells (HTMCs) model. We then developed a new annular sector-shaped microneedle patch (AS-MNs), enabling localized delivery of Nmnat1-LNPs and NAM to the TM. Following application, Nmnat1-LNPs and NAM dual-loaded AS-MNs (Dual@AS-MNs) significantly enhanced the bioavailability of both the Nmnat1 gene and NAM in the TM tissue, leading to a marked reduction in intraocular pressure and alleviation of TM fibrosis in a dexamethasone-induced mice model of glaucoma, highlighting its therapeutic potential. This study presents the first development of an annular sector-shaped microneedle patch as a targeted TM drug delivery platform, and offers a promising new combinatorial strategy for glaucoma treatment. - Source: PubMed
Publication date: 2026/04/27
Huang BaoshanXu WenkaiQiu XinyingYe BaopingWan ZhiyiLuo XinyueFeng BinyueXiang ShengjinNan KaihuiLin Sen - Nicotinamide adenine dinucleotide (NAD) is crucial for cellular functions including DNA repair and metabolism. Nicotinamide mononucleotide adenylyltransferase (NMNAT) enzymes catalyze the final step of NAD synthesis from NMN and ATP. There are three NMNAT isoforms: NMNAT1, NMNAT2, and NMNAT3, located in the nucleus, cytoplasm, and mitochondria, respectively. Nuclear NAD promotes disease progression in NAD-dependent cancers, and it is hypothesized that targeting NMNAT1 with small-molecule inhibitors could be an effective therapeutic strategy. Here, we identify an NMNAT1 inhibitor from a bioactive compound screen and report its effects on NAD levels and the viability of NMNAT1-dependent cancer cell lines. The compound AMI-1 is a known inhibitor of Protein Arginine N-Methyltransferase 1, and we find that it also inhibits NMNAT1 with similar potency. Additionally, we determined a cryo-EM structure of NMNAT1 bound to AMI-1 and revealed its mechanism of inhibition. This provides proof of principle for inhibiting NMNAT1 to target NAD metabolism in dependent cancers, while also highlighting that caution is warranted when interpreting studies using AMI-1 as a PRMT1 inhibitor, given its effect on NAD through NMNAT1. - Source: PubMed
Publication date: 2026/04/08
Lansiquot CarisseWu RuoxiDavies Joanna PSong XiangyangKaniskan H ÜmitJin JianLazarus Michael B - Early-onset inherited retinal degenerations (IRDs), such as Leber congenital amaurosis (LCA) caused by pathogenic variants in the NMNAT1 gene, lead to severe vision loss in children. Despite its ubiquitous expression, reduced NMNAT1 function primarily affects photoreceptor cells (PRs) of the retina, yet the mechanisms underlying their vulnerability remain incompletely understood. Here, we demonstrate that reduced NMNAT1 enzyme function due to the p.V9M mutation leads to DNA damage in PRs, characterized by the progressive accumulation of the oxidative DNA adduct 8-oxo-dG in Nmnat1 mutant mice. Cells with oxidative DNA damage also demonstrate DNA double-strand breaks, as evidenced by co-staining with antibodies to phosphorylated H2AX (γH2A.X). This DNA damage correlates with apoptosis-driven PR degeneration, as evidenced by caspase-9 activation and TUNEL staining in the PRs of the Nmnat1 mutant mice, while alternative cell death pathways such as necroptosis and parthanatos were not significantly activated. Treatment with the antioxidant N-acetylcysteine (NAC) reduced oxidative DNA damage and retinal immune responses, mitigated apoptosis, and preserved cone PRs. Longitudinal assessment via optical coherence tomography (OCT) and electroretinography (ERG) revealed sustained structural and functional protection of the retina in NAC-treated mice. These findings establish oxidative DNA damage as a key driver of PR degeneration in the Nmnat1 model and highlight NAC's potential as a therapeutic strategy for NMNAT1-associated IRD and potentially other IRDs in which oxidative DNA damage contributes to disease pathogenesis. - Source: PubMed
Publication date: 2026/04/02
Zhang HanmengValestil KevinButcher Rossano MPierce Eric A