ArticleThe Journal of experimental medicine2019
3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice.
Article in The Journal of experimental medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
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- An Acebuche Oil-Enriched Diet Prevents Early-Stage Cerebrovascular Alterations in the 5xFAD Mouse Model of Alzheimer's Disease.Nutrients · 2026Article
- BioMedGraphica: An All-in-One Platform for Joint Textual Biomedical Prior Knowledge and Numeric Graph Generation.bioRxiv : the preprint server for biology · 2025Article
- Traumatic Brain Injury and Alzheimer's Disease: A Shared Neurovascular Hypothesis.Neuroscience insights · 2025Review
- Cellular and molecular mechanisms of the blood-brain barrier dysfunction in neurodegenerative diseases.Fluids and barriers of the CNS · 2024Review
- An orthosteric/allosteric bivalent peptide agonist comprising covalently linked protease-activated receptor-derived peptides mimics in vitro and in vivo activities of activated protein C.Journal of thrombosis and haemostasis : JTH · 2024Article
- Single-Cell RNA-seq reveals transcriptomic modulation of Alzheimer's disease by activated protein C.Aging · 2024Article
- Activated protein C signaling mediates neuroinflammation in seizure induced by pilocarpine.Biochemistry and biophysics reports · 2023Article
- Correlation of HIV-Induced Neuroinflammation and Synaptopathy with Impairment of Learning and Memory in Mice with HAND.Journal of clinical medicine · 2023Article
- 3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1β, and Inflammatory Cell Accumulation in the Retina.International journal of molecular sciences · 2023Article
- Thrombin-mediated activation of PAR1 enhances doxorubicin-induced cardiac injury in mice.Blood advances · 2023Article
- Blood-Brain Barrier Dysfunction in Normal Aging and Neurodegeneration: Mechanisms, Impact, and Treatments.Stroke · 2023Review
- Anti-malaria drug artesunate prevents development of amyloid-β pathology in mice by upregulating PICALM at the blood-brain barrier.Molecular neurodegeneration · 2023Article
- Activated protein C in epilepsy pathophysiology.Frontiers in neuroscience · 2023Review
- Blood-brain barrier dysfunction and Alzheimer's disease: associations, pathogenic mechanisms, and therapeutic potential.Frontiers in aging neuroscience · 2023Review
- Reconsidering the role of blood-brain barrier in Alzheimer's disease: From delivery to target.Frontiers in aging neuroscience · 2023Review
- Preserved blood-brain barrier and neurovascular coupling in female 5xFAD model of Alzheimer's disease.Frontiers in aging neuroscience · 2023Article
- Dysregulated haemostasis in thrombo-inflammatory disease.Clinical science (London, England : 1979) · 2022Review
- Activation of Wnt/β-catenin pathway mitigates blood-brain barrier dysfunction in Alzheimer's disease.Brain : a journal of neurology · 2022Article
- 3K3A-Activated Protein C Prevents Microglia Activation, Inhibits NLRP3 Inflammasome and Limits Ocular Inflammation.International journal of molecular sciences · 2022Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
3K3A-activated protein C (APC), a cell-signaling analogue of endogenous blood serine protease APC, exerts vasculoprotective, neuroprotective, and anti-inflammatory activities in rodent models of stroke, brain injury, and neurodegenerative disorders. 3K3A-APC is currently in development as a neuroprotectant in patients with ischemic stroke. Here, we report that 3K3A-APC inhibits BACE1 amyloidogenic pathway in a mouse model of Alzheimer's disease (AD). We show that a 4-mo daily treatment of 3-mo-old 5XFAD mice with murine recombinant 3K3A-APC (100 µg/kg/d i.p.) prevents development of parenchymal and cerebrovascular amyloid-β (Aβ) deposits by 40-50%, which is mediated through NFκB-dependent transcriptional inhibition of BACE1, resulting in blockade of Aβ generation in neurons overexpressing human Aβ-precursor protein. Consistent with reduced Aβ deposition, 3K3A-APC normalized hippocampus-dependent behavioral deficits and cerebral blood flow responses, improved cerebrovascular integrity, and diminished neuroinflammatory responses. Our data suggest that 3K3A-APC holds potential as an effective anti-Aβ prevention therapy for early-stage 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.