ArticlePloS one2014
EphA4 activation of c-Abl mediates synaptic loss and LTP blockade caused by amyloid-β oligomers.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- The Role of c-Abl in Alzheimer's Disease: Guilty or not Guilty?Cellular and molecular neurobiology · 2025Pooled it
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Abl kinase activation promotes axon initial segment disassembly and protein sorting defects in Alzheimer's disease.BMC biology · 2026Article
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Neurexins, Ephrin receptors, and N-cadherin signaling as emerging mechanisms in synaptic dysfunction and neurodegenerative diseases.Communications biology · 2026Review
- Chemical genomics language model toward reliable and explainable compound-protein interaction exploration.Journal of cheminformatics · 2026Article
- The Hippo signaling pathway as a therapeutic target in Alzheimer's disease.Molecular neurodegeneration · 2025Review
- Astrocytic EphA4 signaling is important for the elimination of excitatory synapses in Alzheimer's disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Subclinical infection combined with surgery induced cognitive dysfunction: a novel adult mouse model for perioperative neurocognitive disorder.Frontiers in aging neuroscience · 2025Article
- Transmembrane protein 97 is a potential synaptic amyloid beta receptor in human Alzheimer's disease.Acta neuropathologica · 2024Article
- Lipidation and PEGylation Strategies to Prolong theEuropean journal of medicinal chemistry · 2023Article
- c-Abl Phosphorylates MFN2 to Regulate Mitochondrial Morphology in Cells under Endoplasmic Reticulum and Oxidative Stress, Impacting Cell Survival and Neurodegeneration.Antioxidants (Basel, Switzerland) · 2023Article
- Activation of multiple Eph receptors on neuronal membranes correlates with the onset of optic neuropathy.Eye and vision (London, England) · 2023Article
- Unraveling the Potential of EphA4: A Breakthrough Target and Beacon of Hope for Neurological Diseases.Cellular and molecular neurobiology · 2023Review
- Review
- Activation of Multiple Eph Receptors on Neuronal Membranes Correlates with The Onset of Traumatic Optic Neuropathy.bioRxiv : the preprint server for biology · 2023Article
- c-Abl kinase at the crossroads of healthy synaptic remodeling and synaptic dysfunction in neurodegenerative diseases.Neural regeneration research · 2023Review
- c-Abl tyrosine kinase down-regulation as target for memory improvement in Alzheimer's disease.Frontiers in aging neuroscience · 2023Article
- Super-resolution microscopy: a closer look at synaptic dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2021Review
- Alzheimer's Disease: A Molecular View of β-Amyloid Induced Morbific Events.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The early stages of Alzheimer's disease are characterised by impaired synaptic plasticity and synapse loss. Here, we show that amyloid-β oligomers (AβOs) activate the c-Abl kinase in dendritic spines of cultured hippocampal neurons and that c-Abl kinase activity is required for AβOs-induced synaptic loss. We also show that the EphA4 receptor tyrosine kinase is upstream of c-Abl activation by AβOs. EphA4 tyrosine phosphorylation (activation) is increased in cultured neurons and synaptoneurosomes exposed to AβOs, and in Alzheimer-transgenic mice brain. We do not detect c-Abl activation in EphA4-knockout neurons exposed to AβOs. More interestingly, we demonstrate EphA4/c-Abl activation is a key-signalling event that mediates the synaptic damage induced by AβOs. According to this results, the EphA4 antagonistic peptide KYL and c-Abl inhibitor STI prevented i) dendritic spine reduction, ii) the blocking of LTP induction and iii) neuronal apoptosis caused by AβOs. Moreover, EphA4-/- neurons or sh-EphA4-transfected neurons showed reduced synaptotoxicity by AβOs. Our results are consistent with EphA4 being a novel receptor that mediates synaptic damage induced by AβOs. EphA4/c-Abl signalling could be a relevant pathway involved in the early cognitive decline observed in Alzheimer's disease patients.
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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.