ArticleEMBO reports2024
Hyperfunction of post-synaptic density protein 95 promotes seizure response in early-stage aβ pathology.
Article in EMBO reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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
8 citing papers in PubMed, 6 citations in OpenAlex.
- Novel cell markers with altered expression in brain aging and Alzheimer's disease: A review.IBRO neuroscience reports · 2026Article
- Hyperfunction of PSD-95 leads to hyperexcitability and cognitive abnormalities in MEF2C haploinsufficiency.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- ATF4 Modulates Group 1 mGluR-Dependent molecular signaling, hippocampal plasticity and behavior.Molecular psychiatry · 2026Article
- Effects of UMP, Choline, and Fish Oil on Synaptic Integrity and Motor Coordination in an Alzheimer's Disease Mouse Model.International journal of molecular sciences · 2026Article
- E3 Ubiquitin Ligase Nedd4-2 Exacerbates Seizure-Induced Mitochondrial Defects in an Alzheimer's Disease Mouse Model.Journal of neurochemistry · 2026Article
- Sex-dependent rescue of memory and synaptic deficits in AD model mice by increasing PSD-95 palmitoylation.Communications biology · 2026Article
- Longitudinal pharmacokinetic and safety studies of an antibody-erythropoietin fusion protein for Alzheimer's disease.International journal of pharmaceutics: X · 2025Article
- Alzheimer's Disease and Epilepsy: Exploring Shared Pathways and Promising Biomarkers for Future Treatments.Journal of clinical medicine · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Accumulation of amyloid-beta (Aβ) can lead to the formation of aggregates that contribute to neurodegeneration in Alzheimer's disease (AD). Despite globally reduced neural activity during AD onset, recent studies have suggested that Aβ induces hyperexcitability and seizure-like activity during the early stages of the disease that ultimately exacerbate cognitive decline. However, the underlying mechanism is unknown. Here, we reveal an Aβ-induced elevation of postsynaptic density protein 95 (PSD-95) in cultured neurons in vitro and in an in vivo AD model using APP/PS1 mice at 8 weeks of age. Elevation of PSD-95 occurs as a result of reduced ubiquitination caused by Akt-dependent phosphorylation of E3 ubiquitin ligase murine-double-minute 2 (Mdm2). The elevation of PSD-95 is consistent with the facilitation of excitatory synapses and the surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors induced by Aβ. Inhibition of PSD-95 corrects these Aβ-induced synaptic defects and reduces seizure activity in APP/PS1 mice. Our results demonstrate a mechanism underlying elevated seizure activity during early-stage Aβ pathology and suggest that PSD-95 could be an early biomarker and novel therapeutic target for 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.