ArticleScientific reports2017
Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Glucagon-like peptide 1 (GLP-1) receptor agonists in experimental Alzheimer's disease models: a systematic review and meta-analysis of preclinical studies.Frontiers in pharmacology · 2023Pooled it
- Significance of NAD anabolism profiles in neurological diseases.Metabolic brain disease · 2026Review
- Transcriptional regulation of human NMNAT2: insights from 3D genome sequencing and bioinformatics.The FEBS journal · 2026Article
- The Roles of Moonlighting Nicotinamide Mononucleotide Adenylyl Transferases in Cell Physiology.International journal of molecular sciences · 2025Review
- Caffeine mitigates ROS accumulation and attenuates motor neuron degeneration in the wobbler mouse model of amyotrophic lateral sclerosis.Cell communication and signaling : CCS · 2025Article
- Natural Compounds that Modulate Circadian Rhythms.Current topics in medicinal chemistry · 2025Review
- Inhibitors of NADInternational journal of molecular sciences · 2024Review
- NADAntioxidants & redox signaling · 2023Review
- Molecular differences in brain regional vulnerability to aging between males and females.Frontiers in aging neuroscience · 2023Article
- Selective inhibitors of SARM1 targeting an allosteric cysteine in the autoregulatory ARM domain.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Advances on Therapeutic Strategies for Alzheimer's Disease: From Medicinal Plant to Nanotechnology.Molecules (Basel, Switzerland) · 2022Review
- The key role of the NAD biosynthetic enzyme nicotinamide mononucleotide adenylyltransferase in regulating cell functions.IUBMB life · 2022Review
- Nicotinamide riboside and caffeine partially restore diminished NAD availability but not altered energy metabolism in Alzheimer's disease.Aging cell · 2022Article
- Human Nmnat1 Promotes Autophagic Clearance of Amyloid Plaques in aFrontiers in aging neuroscience · 2022Article
- Nmnat2 attenuates amyloidogenesis and up-regulates ADAM10 in AMPK activity-dependent manner.Aging · 2021Article
- Finding associations in a heterogeneous setting: statistical test for aberration enrichment.Genome medicine · 2021Article
- Vincristine- and bortezomib-induced neuropathies - from bedside to bench and back.Experimental neurology · 2021Review
- The SARM1 axon degeneration pathway: control of the NADCurrent opinion in neurobiology · 2020Review
- Caffeine and NADAntioxidants (Basel, Switzerland) · 2020Article
- Programmed axon degeneration: from mouse to mechanism to medicine.Nature reviews. Neuroscience · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer's, Huntington's, Parkinson's diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.