ArticleThe Journal of experimental medicine2017
SORLA attenuates EphA4 signaling and amyloid β-induced neurodegeneration.
Article in The Journal of experimental medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- SORLA up-regulation suppresses pathological effects in aged tauopathy mouse brain.Science advances · 2026Article
- Amyloid Beta in Alzheimer's Disease: Mechanisms, Biomarker Potential, and Therapeutic Targets.CNS neuroscience & therapeutics · 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
- Common and divergent pathways in early stages of glutamate and tau-mediated toxicities in neurodegeneration.Experimental neurology · 2024Article
- Endo-Lysosomal Network Disorder Reprograms Energy Metabolism in SorL1-Null Rat Hippocampus.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Lipidation and PEGylation Strategies to Prolong theEuropean journal of medicinal chemistry · 2023Article
- Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment.JCI insight · 2023Article
- An Insight into Cellular and Molecular Mechanisms Underlying the Pathogenesis of Neurodegeneration in Alzheimer's Disease.Biomedicines · 2023Review
- Exosomal miR-532-5p induced by long-term exercise rescues blood-brain barrier function in 5XFAD mice via downregulation of EPHA4.Aging cell · 2023Article
- Trem2 deletion enhances tau dispersion and pathology through microglia exosomes.Molecular neurodegeneration · 2022Article
- APOE interacts with ACE2 inhibiting SARS-CoV-2 cellular entry and inflammation in COVID-19 patients.Signal transduction and targeted therapy · 2022Article
- Downregulation of CRTC1 Is Involved in CUMS-Induced Depression-Like Behavior in the Hippocampus and Its RNA Sequencing Analysis.Molecular neurobiology · 2022Article
- The Alzheimer's gene SORL1 is a regulator of endosomal traffic and recycling in human neurons.Cellular and molecular life sciences : CMLS · 2022Article
- The role of Alzheimer's disease risk genes in endolysosomal pathways.Neurobiology of disease · 2022Review
- Roles and Mechanisms of Axon-Guidance Molecules in Alzheimer's Disease.Molecular neurobiology · 2021Review
- Nogo-A-Δ20/EphA4 interaction antagonizes apoptosis of neural stem cells by integrating p38 and JNK MAPK signaling.Journal of molecular histology · 2021Article
- Soluble SORLA Enhances Neurite Outgrowth and Regeneration through Activation of the EGF Receptor/ERK Signaling Axis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer's disease.Molecular neurodegeneration · 2020Review
- RIP at the Synapse and the Role of Intracellular Domains in Neurons.Neuromolecular medicine · 2020Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Sortilin-related receptor with LDLR class A repeats (SORLA, SORL1, or LR11) is a genetic risk factor associated with Alzheimer's disease (AD). Although SORLA is known to regulate trafficking of the amyloid β (Aβ) precursor protein to decrease levels of proteotoxic Aβ oligomers, whether SORLA can counteract synaptic dysfunction induced by Aβ oligomers remains unclear. Here, we show that SORLA interacts with the EphA4 receptor tyrosine kinase and attenuates ephrinA1 ligand-induced EphA4 clustering and activation to limit downstream effects of EphA4 signaling in neurons. Consistent with these findings, SORLA transgenic mice, compared with WT mice, exhibit decreased EphA4 activation and redistribution to postsynaptic densities, with milder deficits in long-term potentiation and memory induced by Aβ oligomers. Importantly, we detected elevated levels of active EphA4 in human AD brains, where EphA4 activation is inversely correlated with SORLA/EphA4 association. These results demonstrate a novel role for SORLA as a physiological and pathological EphA4 modulator, which attenuates synaptotoxic EphA4 activation and cognitive impairment associated with Aβ-induced neurodegeneration 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.