ArticleCell death & disease2016
Extrasynaptic NMDA receptor-induced tau overexpression mediates neuronal death through suppressing survival signaling ERK phosphorylation.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Appraisal of the Neuroprotective Effect of Dexmedetomidine: A Meta-Analysis.Advances in experimental medicine and biology · 2023Pooled it
- Sex-Divergent Patterns in Hippocampal and Cortical NMDA Receptor Density Across the Alzheimer's Disease Continuum.International journal of molecular sciences · 2026Article
- Natural Anti-NMDAR1 autoantibodies associate with slowed decline of cognitive functions in Alzheimer's diseases.Translational psychiatry · 2026Article
- Ceftriaxone alleviates mitochondrial damage through the inhibition of extrasynaptic NMDA receptor-mediated changes in intracellular calcium levels to improve cognitive deficits in APP/PS1 mice.Alzheimer's research & therapy · 2025Article
- Future Perspectives of NMDAR in CNS Disorders.Molecules (Basel, Switzerland) · 2025Review
- NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic Membranes.International journal of molecular sciences · 2024Review
- Tau modulation through AAV9 therapy augments Akt/Erk survival signalling in glaucoma mitigating the retinal degenerative phenotype.Acta neuropathologica communications · 2024Article
- LncRNA ENST00000440246.1 Promotes Alzheimer's Disease Progression by Targeting PP2A.Biochemical genetics · 2024Article
- Familial Alzheimer's Disease Neurons Bearing Mutations inLife (Basel, Switzerland) · 2024Article
- Extrasynaptic NMDA receptors in acute and chronic excitotoxicity: implications for preventive treatments of ischemic stroke and late-onset Alzheimer's disease.Molecular neurodegeneration · 2023Review
- Do tau-synaptic long-term depression interactions in the hippocampus play a pivotal role in the progression of Alzheimer's disease?Neural regeneration research · 2023Review
- Alzheimer's Disease and Impaired Bone Microarchitecture, Regeneration and Potential Genetic Links.Life (Basel, Switzerland) · 2023Review
- Using ΔK280 TauBiomolecules · 2023Article
- Pinostrobin from Boesenbergia rotunda attenuates oxidative stress and promotes functional recovery in rat model of sciatic nerve crush injury.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Article
- Inhibition of CK2 mitigates Alzheimer's tau pathology by preventing NR2B synaptic mislocalization.Acta neuropathologica communications · 2022Article
- Long-Term Depression-Inducing Low Frequency Stimulation Enhances p-Tau181 and p-Tau217 in an Age-Dependent Manner in Live Rats.Journal of Alzheimer's disease : JAD · 2022Article
- Tau Acts in Concert With Kinase/Phosphatase Underlying Synaptic Dysfunction.Frontiers in aging neuroscience · 2022Review
- Functional Neurophysiological Biomarkers of Early-Stage Alzheimer's Disease: A Perspective of Network Hyperexcitability in Disease Progression.Journal of Alzheimer's disease : JAD · 2022Review
- Retinal ganglion cell loss in an ex vivo mouse model of optic nerve cut is prevented by curcumin treatment.Cell death discovery · 2021Article
- Building a Bridge Between NMDAR-Mediated Excitotoxicity and Mitochondrial Dysfunction in Chronic and Acute Diseases.Cellular and molecular neurobiology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular accumulation of the hyperphosphorylated tau is a pathological hallmark in the brain of Alzheimer disease. Activation of extrasynaptic NMDA receptors (E-NMDARs) induces excitatory toxicity that is involved in Alzheimer's neurodegeneration. However, the intrinsic link between E-NMDARs and the tau-induced neuronal damage remains elusive. In the present study, we showed in cultured primary cortical neurons that activation of E-NMDA receptors but not synaptic NMDA receptors dramatically increased tau mRNA and protein levels, with a simultaneous neuronal degeneration and decreased neuronal survival. Memantine, a selective antagonist of E-NMDARs, reversed E-NMDARs-induced tau overexpression. Activation of E-NMDARs in wild-type mouse brains resulted in neuron loss in hippocampus, whereas tau deletion in neuronal cultures and in the mouse brains rescued the E-NMDARs-induced neuronal death and degeneration. The E-NMDARs-induced tau overexpression was correlated with a reduced ERK phosphorylation, whereas the increased MEK activity, decreased binding and activity of ERK phosphatase to ERK, and increased ERK phosphorylation were observed in tau knockout mice. On the contrary, addition of tau proteins promoted ERK dephosphorylation in vitro. Taking together, these results indicate that tau overexpression mediates the excitatory toxicity induced by E-NMDAR activation through inhibiting ERK phosphorylation.
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