ArticleCommunications biology2019
Dysfunction of the ubiquitin ligase E3A Ube3A/E6-AP contributes to synaptic pathology in Alzheimer's disease.
Article in Communications biology, 2019. 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Diverse Transcriptional Alterations in V2a Propriospinal Neurons Following Spinal Cord Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Perinatal Choline Supplementation Promotes Resilience Against Progression of Alzheimer's Disease-Like Brain Transcriptomic Signatures in AppAging cell · 2025Article
- The E3 ligase MEX3B forms a tripartite complex withOpen biology · 2025Article
- Impaired Proteostasis is Linked to Neurological Pathology in a Zebrafish NGLY1 Deficiency Model.Journal of inherited metabolic disease · 2025Article
- Roles of Ubiquitin Ligases and Deubiquitylases in Alzheimer's Disease.Molecular neurobiology · 2025Review
- Activity-dependent regulation of Cdc42 by Ephexin5 drives synapse growth and stabilization.Science advances · 2025Article
- Unraveling the Roles of UBE3A in Neurodevelopment and Neurodegeneration.International journal of molecular sciences · 2025Review
- The ubiquitin-proteasome system in Alzheimer's disease: mechanism of action and current status of treatment.Frontiers in aging neuroscience · 2025Review
- Pirh2 modulates the mitochondrial function and cytochrome c-mediated neuronal death during Alzheimer's disease.Cell death & disease · 2024Article
- Review
- MicroRNA-375 restrains the progression of lung squamous cell carcinoma by modulating the ERK pathway via UBE3A-mediated DUSP1 degradation.Cell death discovery · 2023Article
- A heterozygous mutation in UBE2H in a patient with developmental delay leads to an aberrant brain development in zebrafish.Human genomics · 2023Article
- The Labyrinthine Landscape of APP Processing: State of the Art and Possible Novel Soluble APP-Related Molecular Players in Traumatic Brain Injury and Neurodegeneration.International journal of molecular sciences · 2023Article
- c-Abl kinase at the crossroads of healthy synaptic remodeling and synaptic dysfunction in neurodegenerative diseases.Neural regeneration research · 2023Review
- A Genome-Wide Functional Screen Identifies Enhancer and Protective Genes for Amyloid Beta-Peptide Toxicity.International journal of molecular sciences · 2023Article
- Neurodevelopmental disorders and microcephaly: how apoptosis, the cell cycle, tau and amyloid-β precursor protein APPly.Frontiers in molecular neuroscience · 2023Review
- Ubiquitin and Ubiquitin-like Proteins in Cancer, Neurodegenerative Disorders, and Heart Diseases.International journal of molecular sciences · 2022Review
- Rac-maninoff and Rho-vel: The symphony of Rho-GTPase signaling at excitatory synapses.Small GTPases · 2022Article
- Symptomatic, Genetic, and Mechanistic Overlaps between Autism and Alzheimer's Disease.Biomolecules · 2021Review
- Deleting a UBE3A substrate rescues impaired hippocampal physiology and learning in Angelman syndrome mice.Scientific reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synaptic dysfunction and synapse loss are prominent features in Alzheimer's disease. Members of the Rho-family of guanosine triphosphatases, specifically RhoA, and the synaptic protein Arc are implicated in these pathogenic processes. They share a common regulatory molecule, the E3 ligase Ube3A/E6-AP. Here, we show that Ube3A is reduced in an Alzheimer's disease mouse model, Tg2576 mouse, which overexpresses human APP695 carrying the Swedish mutation, and accumulates Aβ in the brain. Depletion of Ube3A precedes the age-dependent behavioral deficits and loss of dendritic spines in these mice, and results from a decrease in solubility following phosphorylation by c-Abl, after Aβ exposure. Loss of Ube3A triggers the accumulation of Arc and Ephexin-5, driving internalization of GluR1, and activation of RhoA, respectively, culminating in pruning of synapses, which is blocked by restoring Ube3A. Taken together, our results place Ube3A as a critical player in Alzheimer's disease pathogenesis, and as a potential therapeutic target.
Indexed as
Identifiers
What OpenQuestion holds
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.