ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2020
Urokinase-Type Plasminogen Activator Protects Cerebral Cortical Neurons from Soluble Aβ-Induced Synaptic Damage.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 25 citations in OpenAlex.
- uPAR exhibits age- and region-dependent expression in the brains of mice with Alzheimer's disease-like pathology.Brain research · 2026Article
- Novel Roles of Urokinase- and Tissue-Type Plasminogen Activators in Substance Use Disorders: A Narrative Review of Molecular Mechanisms and Translational Perspectives.International journal of molecular sciences · 2026Review
- The Double-Edged Sword Effect of the Fibrinolytic System in Alzheimer's Disease.Cellular and molecular neurobiology · 2026Review
- Novel mouse line with D277N mutation in theFrontiers in cell and developmental biology · 2026Article
- Causal association of plasminogen activators and their inhibitors with Alzheimer's disease: a Mendelian randomization study.Archives of medical science : AMS · 2025Article
- Cold Inducible RNA-Binding Protein Promotes the Development of Alzheimer's Disease Partly by Inhibition of uPA in Astrocytes.Degenerative neurological and neuromuscular disease · 2024Article
- Pharmacological inhibition of plasminogen activator inhibitor-1 prevents memory deficits and reduces neuropathology in APP/PS1 mice.Psychopharmacology · 2023Article
- Common Genetic Factors and Pathways in Alzheimer's Disease and Ischemic Stroke: Evidences from GWAS.Genes · 2023Review
- Effects of copy number variations on longevity in late-onset Alzheimer's disease patients: insights from a causality network analysis.Frontiers in aging neuroscience · 2023Article
- The uPA/uPAR system in astrocytic wound healing.Neural regeneration research · 2022Review
- Review of evidence implicating the plasminogen activator system in blood-brain barrier dysfunction associated with Alzheimer's disease.Ageing and neurodegenerative diseases · 2022Article
- The plasminogen activating system in the pathogenesis of Alzheimer's disease.Neural regeneration research · 2021Review
- Urokinase-type plasminogen activator promotes N-cadherin-mediated synaptic recovery in the ischemic brain.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Hemostasis components in cerebral amyloid angiopathy and Alzheimer's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Review
- Urokinase-type plasminogen activator-mediated crosstalk between N-cadherin and β-catenin promotes wound healing.Journal of cell science · 2021Article
- Plasminogen Activators in Neurovascular and Neurodegenerative Disorders.International journal of molecular sciences · 2021Review
- Preparation of Synaptoneurosomes to Study the Synapse in the Murine Cerebral Cortex.Bio-protocol · 2021Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Soluble amyloid β (Aβ)-induced synaptic dysfunction is an early event in the pathogenesis of Alzheimer's disease (AD) that precedes the deposition of insoluble Aβ and correlates with the development of cognitive deficits better than the number of plaques. The mammalian plasminogen activation (PA) system catalyzes the generation of plasmin via two activators: tissue-type (tPA) and urokinase-type (uPA). A dysfunctional tPA-plasmin system causes defective proteolytic degradation of Aβ plaques in advanced stages of AD. In contrast, it is unknown whether uPA and its receptor (uPAR) contribute to the pathogenesis of this disease. Neuronal cadherin (NCAD) plays a pivotal role in the formation of synapses and dendritic branches, and Aβ decreases its expression in cerebral cortical neurons. Here we show that neuronal uPA protects the synapse from the harmful effects of soluble Aβ. However, Aβ-induced inactivation of the eukaryotic initiation factor 2α halts the transcription of uPA mRNA, leaving unopposed the deleterious effects of Aβ on the synapse. In line with these observations, the synaptic abundance of uPA, but not uPAR, is decreased in the frontal cortex of AD patients and 5xFAD mice, and in cerebral cortical neurons incubated with soluble Aβ. We found that uPA treatment increases the synaptic expression of NCAD by a uPAR-mediated plasmin-independent mechanism, and that uPA-induced formation of NCAD dimers protects the synapse from the harmful effects of soluble Aβ oligomers. These data indicate that Aβ-induced decrease in the synaptic abundance of uPA contributes to the development of synaptic damage in the early stages of AD.
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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.