ArticleeLife2017
Physiological and pathophysiological control of synaptic GluN2B-NMDA receptors by the C-terminal domain of amyloid precursor protein.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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Who cites it
23 citing papers in PubMed.
- Modeling Alzheimer's Disease: A Review of Gene-Modified and Induced Animal Models, Complex Cell Culture Models, and Computational Modeling.Brain sciences · 2025Review
- The AICD interactome: implications in neurodevelopment and neurodegeneration.Biochemical Society transactions · 2024Review
- Article
- The amyloid precursor protein intracellular domain induces sleep disruptions and its nuclear localization fluctuates in circadian pacemaker neurons in Drosophila and mice.Neurobiology of disease · 2024Article
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- Article
- A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics.eLife · 2023Article
- Spinophilin-dependent regulation of GluN2B-containing NMDAR-dependent calcium influx, GluN2B surface expression, and cleaved caspase expression.Synapse (New York, N.Y.) · 2023Article
- Age-dependent NMDA receptor function is regulated by the amyloid precursor protein.Aging cell · 2023Article
- GluN2B-NMDAR subunit contribution on synaptic plasticity: A phenomenological model for CA3-CA1 synapses.Frontiers in synaptic neuroscience · 2023Article
- Altered synaptic plasticity at hippocampal CA1-CA3 synapses in Alzheimer's disease: integration of amyloid precursor protein intracellular domain and amyloid beta effects into computational models.Frontiers in computational neuroscience · 2023Article
- The amyloid precursor protein: a converging point in Alzheimer's disease.Molecular neurobiology · 2022Review
- Pathological and neurophysiological outcomes of seeding human-derived tau pathology in the APP-KI NL-G-F and NL-NL mouse models of Alzheimer's Disease.Acta neuropathologica communications · 2022Article
- Regulation of PPARα by APP in Alzheimer disease affects the pharmacological modulation of synaptic activity.JCI insight · 2021Article
- Pathophysiological Ionotropic Glutamate Signalling in Neuroinflammatory Disease as a Therapeutic Target.Frontiers in neuroscience · 2021Review
- Analysis of Age-Dependent Alterations in Excitability Properties of CA1 Pyramidal Neurons in an APPPS1 Model of Alzheimer's Disease.Frontiers in aging neuroscience · 2021Article
- SK2 channel regulation of neuronal excitability, synaptic transmission, and brain rhythmic activity in health and diseases.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Age-related shift in LTD is dependent on neuronal adenosine AMolecular psychiatry · 2020Article
- Amyloid, APP, and Electrical Activity of the Brain.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2020Review
- Hippocampal Deficits in Amyloid-β-Related Rodent Models of Alzheimer's Disease.Frontiers in neuroscience · 2020Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amyloid precursor protein (APP) harbors physiological roles at synapses and is central to Alzheimer's disease (AD) pathogenesis. Evidence suggests that APP intracellular domain (AICD) could regulate synapse function, but the underlying molecular mechanisms remain unknown. We addressed AICD actions at synapses, per se, combining in vivo AICD expression, ex vivo AICD delivery or APP knock-down by in utero electroporation of shRNAs with whole-cell electrophysiology. We report a critical physiological role of AICD in controlling GluN2B-containing NMDA receptors (NMDARs) at immature excitatory synapses, via a transcription-dependent mechanism. We further show that AICD increase in mature neurons, as reported in AD, alters synaptic NMDAR composition to an immature-like GluN2B-rich profile. This disrupts synaptic signal integration, via over-activation of SK channels, and synapse plasticity, phenotypes rescued by GluN2B antagonism. We provide a new physiological role for AICD, which becomes pathological upon AICD increase in mature neurons. Thus, AICD could contribute to AD synaptic failure.
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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 Socratic graph.