ArticleJournal of Alzheimer's disease : JAD2018
Amyloid-β Induces AMPA Receptor Ubiquitination and Degradation in Primary Neurons and Human Brains of Alzheimer's Disease.
Article in Journal of Alzheimer's disease : JAD, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 3 of them syntheses that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 3 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- The Emerging Roles of E3 Ligases and DUBs in Neurodegenerative Diseases.Molecular neurobiology · 2023Pooled it
- Whole-genome sequencing reveals novel ethnicity-specific rare variants associated with Alzheimer's disease.Molecular psychiatry · 2022Pooled it
- The Amyloid-β Pathway in Alzheimer's Disease.Molecular psychiatry · 2021Pooled it
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Phytochemicals with potential NMDAR-inhibitory activities: a review of neuroprotective mechanisms against excitotoxicity.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Review
- The interaction between neurotransmitter receptor activity and amyloid-β pathology in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Review
- ADAR2-mediated Q/R editing of GluA2 in homeostatic synaptic plasticity.Science signaling · 2025Article
- AMPA receptors in the evolving synapse: structure, function, and disease implications.Frontiers in synaptic neuroscience · 2025Review
- Hippocampal Synaptic Plasticity: Integrating Memory and Anxiety Impairments in the Early Stages of Alzheimer's Disease.Current topics in behavioral neurosciences · 2025Review
- DUBs in Alzheimer's disease: mechanisms and therapeutic implications.Cell death discovery · 2024Review
- Photobiomodulation in experimental models of Alzheimer's disease: state-of-the-art and translational perspectives.Alzheimer's research & therapy · 2024Review
- Fluorescence lifetime imaging of AMPA receptor endocytosis in living neurons: effects of Aβ and PP1.Frontiers in molecular neuroscience · 2024Article
- Involvement of ubiquitination in Alzheimer's disease.Frontiers in neurology · 2024Review
- Molecular Mechanisms of AMPA Receptor Trafficking in the Nervous System.International journal of molecular sciences · 2023Review
- 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
- Ubiquitination of the GluA1 Subunit of AMPA Receptors Is Required for Synaptic Plasticity, Memory, and Cognitive Flexibility.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Amyloid β-based therapy for Alzheimer's disease: challenges, successes and future.Signal transduction and targeted therapy · 2023Review
- Lipoprotein Metabolism, Protein Aggregation, and Alzheimer's Disease: A Literature Review.International journal of molecular sciences · 2023Review
- Proposed mechanisms of tau: relationships to traumatic brain injury, Alzheimer's disease, and epilepsy.Frontiers in neurology · 2023Article
- The broad-spectrum activity of perampanel: state of the art and future perspective of AMPA antagonism beyond epilepsy.Frontiers in neurology · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
As the primary mediator for synaptic transmission, AMPA receptors (AMPARs) are crucial for synaptic plasticity and higher brain functions. A downregulation of AMPAR expression has been indicated as one of the early pathological molecular alterations in Alzheimer's disease (AD), presumably via amyloid-β (Aβ). However, the molecular mechanisms leading to the loss of AMPARs remain less clear. We report that in primary neurons, application of Aβ triggers AMPAR internalization accompanied with a decrease in cell-surface AMPAR expression. Importantly, in both Aβ-treated neurons and human brain tissue from AD patients, we observed a significant decrease in total AMPAR amount and an enhancement in AMPAR ubiquitination. Consistent with facilitated receptor degradation, AMPARs show higher turnover rates in the presence of Aβ. Furthermore, AD brain lysates and Aβ-incubated neurons show increased expression of the AMPAR E3 ligase Nedd4 and decreased expression of AMPAR deubiquitinase USP46. Changes in these enzymes are responsible for the Aβ-dependent AMPAR reduction. These findings indicate that AMPAR ubiquitination acts as the key molecular event leading to the loss of AMPARs and thus suppressed synaptic transmission in AD.
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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.