ArticleThe Journal of biological chemistry2010
Inhibition of calcineurin-mediated endocytosis and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors prevents amyloid beta oligomer-induced synaptic disruption.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 183 citations in OpenAlex.
- Residue-Specific Incorporation of Noncanonical Amino Acids in Auxotrophic Hosts:Chemical reviews · 2025Review
- Investigating the Impact of NMDA Receptor Organization and Biological Sex in the APPswe/PS1dE9 Mouse Model of Alzheimer's Disease.International journal of molecular sciences · 2025Article
- AMPA receptor diffusional trapping machinery as an early therapeutic target in neurodegenerative and neuropsychiatric disorders.Translational neurodegeneration · 2025Review
- Multiplexed expansion revealing for imaging multiprotein nanostructures in healthy and diseased brain.Nature communications · 2024Article
- Early hippocampal hyperexcitability and synaptic reorganization in mouse models of amyloidosis.iScience · 2024Article
- Amyloid-β Causes NMDA Receptor Dysfunction and Dendritic Spine Loss through mGluR1 and AKAP150-Anchored Calcineurin Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Alzheimer-like behavior and synaptic dysfunction in 3 × Tg-AD mice are reversed with calcineurin inhibition.Experimental brain research · 2024Article
- Photobiomodulation in experimental models of Alzheimer's disease: state-of-the-art and translational perspectives.Alzheimer's research & therapy · 2024Review
- Ca2+-PP2B-PSD-95 axis: A novel regulatory mechanism of the phosphorylation state of Serine 295 of PSD-95.PloS one · 2024Article
- Neurotoxic β-amyloid oligomers cause mitochondrial dysfunction-the trigger for PANoptosis in neurons.Frontiers in aging neuroscience · 2024Review
- Impairments in endogenous AMPA receptor dynamics correlates with learning deficits in Alzheimer's disease model mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Current understanding of metal-dependent amyloid-β aggregation and toxicity.RSC chemical biology · 2023Review
- Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer's disease: Mechanistic insights and potential therapies.Frontiers in neural circuits · 2023Review
- MiR-142-3p is a Critical Modulator of TNF-mediated Neuronal Toxicity in Multiple Sclerosis.Current neuropharmacology · 2023Article
- The Transcranial Light Therapy Improves Synaptic Plasticity in the Alzheimer's Disease Mouse Model.Brain sciences · 2022Article
- Bioactive human Alzheimer brain soluble Aβ: pathophysiology and therapeutic opportunities.Molecular psychiatry · 2022Review
- Calcineurin in development and disease.Genes & diseases · 2022Review
- A Class I HDAC Inhibitor Rescues Synaptic Damage and Neuron Loss in APP-Transfected Cells and APP/PS1 Mice through the GRIP1/AMPA Pathway.Molecules (Basel, Switzerland) · 2022Article
- Significance of GABAInternational journal of molecular sciences · 2021Review
- β-Amyloid disruption of LTP/LTD balance is mediated by AKAP150-anchored PKA and Calcineurin regulation of CaCell reports · 2021Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synaptic degeneration, including impairment of synaptic plasticity and loss of synapses, is an important feature of Alzheimer disease pathogenesis. Increasing evidence suggests that these degenerative synaptic changes are associated with an accumulation of soluble oligomeric assemblies of amyloid beta (Abeta) known as ADDLs. In primary hippocampal cultures ADDLs bind to a subpopulation of neurons. However the molecular basis of this cell type-selective interaction is not understood. Here, using siRNA screening technology, we identified alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits and calcineurin as candidate genes potentially involved in ADDL-neuron interactions. Immunocolocalization experiments confirmed that ADDL binding occurs in dendritic spines that express surface AMPA receptors, particularly the calcium-impermeable type II AMPA receptor subunit (GluR2). Pharmacological removal of the surface AMPA receptors or inhibition of AMPA receptors with antagonists reduces ADDL binding. Furthermore, using co-immunoprecipitation and photoreactive amino acid cross-linking, we found that ADDLs interact preferentially with GluR2-containing complexes. We demonstrate that calcineurin mediates an endocytotic process that is responsible for the rapid internalization of bound ADDLs along with surface AMPA receptor subunits, which then both colocalize with cpg2, a molecule localized specifically at the postsynaptic endocytic zone of excitatory synapses that plays an important role in activity-dependent glutamate receptor endocytosis. Both AMPA receptor and calcineurin inhibitors prevent oligomer-induced surface AMPAR and spine loss. These results support a model of disease pathogenesis in which Abeta oligomers interact selectively with neurotransmission pathways at excitatory synapses, resulting in synaptic loss via facilitated endocytosis. Validation of this model in human disease would identify therapeutic targets for Alzheimer disease.
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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.