ArticlePloS one2009
Disassembly of shank and homer synaptic clusters is driven by soluble beta-amyloid(1-40) through divergent NMDAR-dependent signalling pathways.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 83 citations in OpenAlex.
- Targeting TTLL1 Alleviates Aβ-Induced Microtubule Disruption and TAU Pathology in Human iPSC-Derived Cortical Neurons.Pharmaceutics · 2026Article
- 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
- Synaptic Compensatory Plasticity in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Review
- Postsynaptic Protein Shank3a Deficiency Synergizes with Alzheimer's Disease Neuropathology to Impair Cognitive Performance in the 3xTg-AD Murine Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Shank2 identifies a subset of glycinergic neurons involved in altered nociception in an autism model.Molecular autism · 2023Article
- SorCS1 inhibits amyloid-β binding to neurexin and rescues amyloid-β-induced synaptic pathology.Life science alliance · 2023Article
- Association of SHANK Family with Neuropsychiatric Disorders: An Update on Genetic and Animal Model Discoveries.Cellular and molecular neurobiology · 2022Review
- Synaptic restoration by cAMP/PKA drives activity-dependent neuroprotection to motoneurons in ALS.The Journal of experimental medicine · 2020Article
- Novel huperzine A based NMDA antagonists: insights from molecular docking, ADME/T and molecular dynamics simulation studies.RSC advances · 2020Article
- Calcium-Handling Defects and Neurodegenerative Disease.Cold Spring Harbor perspectives in biology · 2020Review
- Early-Occurring Dendritic Spines Alterations in Mouse Models of Alzheimer's Disease Inform on Primary Causes of Neurodegeneration.Frontiers in synaptic neuroscience · 2020Review
- The epilepsy and intellectual disability-associated protein TBC1D24 regulates the maintenance of excitatory synapses and animal behaviors.PLoS genetics · 2020Article
- Altered microRNAs related to synaptic function as potential plasma biomarkers for Alzheimer's disease.Alzheimer's research & therapy · 2019Article
- Emergence of synaptic and cognitive impairment in a mature-onset APP mouse model of Alzheimer's disease.Acta neuropathologica communications · 2019Article
- Nutrient limitation affects presynaptic structures through dissociable Bassoon autophagic degradation and impaired vesicle release.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Article
- Protective effects ofNeural regeneration research · 2017Article
- Cellular prion protein as a receptor for amyloid-β oligomers in Alzheimer's disease.Biochemical and biophysical research communications · 2017Review
- Amyloid-β Oligomers Interact with Neurexin and Diminish Neurexin-mediated Excitatory Presynaptic Organization.Scientific reports · 2017Article
- Treating the Synapse in Major Psychiatric Disorders: The Role of Postsynaptic Density Network in Dopamine-Glutamate Interplay and Psychopharmacologic Drugs Molecular Actions.International journal of molecular sciences · 2017Review
- Role of BACE1 in Alzheimer's synaptic function.Translational neurodegeneration · 2017Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Disruption of the postsynaptic density (PSD), a network of scaffold proteins located in dendritic spines, is thought to be responsible for synaptic dysfunction and loss in early-stage Alzheimer's disease (AD). Extending our previous demonstration that derangement of the PSD by soluble amyloid-beta (Abeta) involves proteasomal degradation of PSD-95, a protein important for ionotropic glutamate receptor trafficking, we now show that Abeta also disrupts two other scaffold proteins, Homer1b and Shank1, that couple PSD-95 with ionotropic and metabotropic glutamate receptors. Treatment of fronto-cortical neurons with soluble Abeta results in rapid (within 1 h) and significant thinning of the PSD, decreased synaptic levels of Homer1b and Shank1, and reduced synaptic mGluR1 levels. We show that de novo protein synthesis is required for the declustering effects of Abeta on Homer1b (but not Shank1) and that, in contrast to PSD-95, Abeta-induced Homer1b and Shank1 cluster disassembly does not depend on proteasome activity. The regulation of Homer1b and Shank1 by Abeta diverges in two other respects: i) whereas the activity of both NMDAR and VDCC is required for Abeta-induced declustering of Homer1b, Abeta-induced declustering of Shank1 only requires NMDAR activity; and ii) whereas the effects of Abeta on Homer1b involve engagement of the PI-3K pathway and calcineurin phosphatase (PP2B) activity, those on Shank1 involve activation of the ERK pathway. In summary, soluble Abeta recruits discrete signalling pathways to rapidly reduce the synaptic localization of major components of the PSD and to regulate the availability of mGluR1 in the synapse.
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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 OpenQuestion graph.