ArticleHuman molecular genetics2012
CREB-activity and nmnat2 transcription are down-regulated prior to neurodegeneration, while NMNAT2 over-expression is neuroprotective, in a mouse model of human tauopathy.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 107 citations in OpenAlex.
- 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
- NAD⁺ Reduction in Glutamatergic Neurons Induces Lipid Catabolism and Neuroinflammation in the Brain via SARM1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Roles of Moonlighting Nicotinamide Mononucleotide Adenylyl Transferases in Cell Physiology.International journal of molecular sciences · 2025Review
- NMNAT2 is a druggable target to drive neuronal NAD production.Nature communications · 2024Article
- An Update on the Potential of Tangeretin in the Management of Neuroinflammation-Mediated Neurodegenerative Disorders.Life (Basel, Switzerland) · 2024Review
- NMNAT2 supports vesicular glycolysis via NAD homeostasis to fuel fast axonal transport.Molecular neurodegeneration · 2024Article
- Role of NADCellular and molecular neurobiology · 2023Review
- NADAntioxidants (Basel, Switzerland) · 2023Review
- Molecular differences in brain regional vulnerability to aging between males and females.Frontiers in aging neuroscience · 2023Article
- From cradle to grave: neurogenesis, neuroregeneration and neurodegeneration in Alzheimer's and Parkinson's diseases.Neural regeneration research · 2022Review
- Protective effects of NAMPT or MAPK inhibitors and NaR on Wallerian degeneration of mammalian axons.Neurobiology of disease · 2022Article
- The key role of the NAD biosynthetic enzyme nicotinamide mononucleotide adenylyltransferase in regulating cell functions.IUBMB life · 2022Review
- The mouse nicotinamide mononucleotide adenylyltransferase chaperones diverse pathological amyloid client proteins.The Journal of biological chemistry · 2022Article
- Human Nmnat1 Promotes Autophagic Clearance of Amyloid Plaques in aFrontiers in aging neuroscience · 2022Article
- Sarm1 haploinsufficiency or low expression levels after antisense oligonucleotides delay programmed axon degeneration.Cell reports · 2021Article
- Nmnat2 attenuates amyloidogenesis and up-regulates ADAM10 in AMPK activity-dependent manner.Aging · 2021Article
- Systematic analysis of purified astrocytes after SCI unveils Zeb2os function during astrogliosis.Cell reports · 2021Article
- Neuronal NMNAT2 Overexpression Does Not Achieve Significant Neuroprotection in Experimental Autoimmune Encephalomyelitis/Optic Neuritis.Frontiers in cellular neuroscience · 2021Article
- Mitochondrial Behavior in Axon Degeneration and Regeneration.Frontiers in aging neuroscience · 2021Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Tauopathies, characterized by neurofibrillary tangles (NFTs) of phosphorylated tau proteins, are a group of neurodegenerative diseases, including frontotemporal dementia and both sporadic and familial Alzheimer's disease. Forebrain-specific over-expression of human tau(P301L), a mutation associated with frontotemporal dementia with parkinsonism linked to chromosome 17, in rTg4510 mice results in the formation of NFTs, learning and memory impairment and massive neuronal death. Here, we show that the mRNA and protein levels of NMNAT2 (nicotinamide mononucleotide adenylyltransferase 2), a recently identified survival factor for maintaining neuronal health in peripheral nerves, are reduced in rTg4510 mice prior to the onset of neurodegeneration or cognitive deficits. Two functional cAMP-response elements (CREs) were identified in the nmnat2 promoter region. Both the total amount of phospho-CRE binding protein (CREB) and the pCREB bound to nmnat2 CRE sites in the cortex and the hippocampus of rTg4510 mice are significantly reduced, suggesting that NMNAT2 is a direct target of CREB under physiological conditions and that tau(P301L) overexpression down-regulates CREB-mediated transcription. We found that over-expressing NMNAT2 or its homolog NMNAT1, but not NMNAT3, in rTg4510 hippocampi from 6 weeks of age using recombinant adeno-associated viral vectors significantly reduced neurodegeneration caused by tau(P301L) over-expression at 5 months of age. In summary, our studies strongly support a protective role of NMNAT2 in the mammalian central nervous system. Decreased endogenous NMNAT2 function caused by reduced CREB signaling during pathological insults may be one of underlying mechanisms for neuronal death in tauopathies.
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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.