ArticleAnnals of clinical and translational neurology2017
NMNAT3 is protective against the effects of neonatal cerebral hypoxia-ischemia.
Article in Annals of clinical and translational neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.Acta pharmacologica Sinica · 2025Review
- The Roles of Moonlighting Nicotinamide Mononucleotide Adenylyl Transferases in Cell Physiology.International journal of molecular sciences · 2025Review
- Article
- Impacts of Polyenvironmental Factors on DNA Methylation in Patients With Psychosis.Schizophrenia bulletin open · 2025Article
- Pathobiochemistry of Aging and Neurodegeneration: Deregulation of NAD+ Metabolism in Brain Cells.Biomolecules · 2024Review
- Axonal energy metabolism, and the effects in aging and neurodegenerative diseases.Molecular neurodegeneration · 2023Review
- Functional neuropathology of neonatal hypoxia-ischemia by single-mouse longitudinal electroencephalography.Epilepsia · 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
- Whole-Genome Methylation Analysis Revealed ART-Specific DNA Methylation Pattern of Neuro- and Immune-System Pathways in Chinese Human Neonates.Frontiers in genetics · 2021Article
- Regulation of degenerative spheroids after injury.Scientific reports · 2020Article
- [Effects of nicotinamide mononucleotide adenylyl transferase 3 on mitochondrial function and anti-oxidative stress of rabbit bone marrow mesenchymal stem cells via regulating nicotinamide adenine dinucleotide levels].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2020Article
- Positive and negative conditioning in the neonatal brain.Conditioning medicine · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveTo determine whether the NAD+ biosynthetic protein, nicotinamide mononucleotide adenylyltransferase-3 (NMNAT3), is a neuroprotective inducible enzyme capable of decreasing cerebral injury after neonatal hypoxia-ischemia (H-I) and reducing glutamate receptor-mediated excitotoxic neurodegeneration of immature neurons.
methodsUsing NMNAT3-overexpressing mice we investigated whether increases in brain NMNAT3 reduced cerebral tissue loss following H-I. We then employed biochemical methods from injured neonatal brains to examine the inducibility of NMNAT3 and the mechanism of NMNAT3-dependent neuroprotection. Using AAV8-mediated vectors for in vitro neuronal NMNAT3 knockdown, we then examine the endogenous role of this protein on immature neuronal survival prior and following NMDA receptor-mediated excitotoxicity.
resultsNMNAT3 mRNA and protein levels increased after neonatal H-I. In addition, NMNAT3 overexpression decreased cortical and hippocampal tissue loss 7 days following injury. We further show that the NMNAT3 neuroprotective mechanism involves a decrease in calpastatin degradation, and a decrease in caspase-3 activity and calpain-mediated cleavage. Conversely, NMNAT3 knockdown of cortical and hippocampal neurons in vitro caused neuronal degeneration and increased excitotoxic cell death. The neurodegenerative effects of NMNAT3 knockdown were counteracted by exogenous upregulation of NMNAT3.
conclusionsOur observations provide new insights into the neuroprotective mechanisms of NMNATs in the injured developing brain, adding NMNAT3 as an important neuroprotective enzyme in neonatal H-I via inhibition of apoptotic and necrotic neurodegeneration. Interestingly, we find that endogenous NMNAT3 is an inducible protein important for maintaining the survival of immature neurons. Future studies aimed at uncovering the mechanisms of NMNAT3 upregulation and neuroprotection may offer new therapies against the effects of hypoxic-ischemic encephalopathy.
Identifiers
What OpenQuestion holds
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.