ArticleThe European journal of neuroscience2009
Neuroprotective activities of activated protein C mutant with reduced anticoagulant activity.
Article in The European journal of neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 53 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
53 citing papers in PubMed, 83 citations in OpenAlex.
- Trial
- Phase 1 safety, tolerability and pharmacokinetics of 3K3A-APC in healthy adult volunteers.Current pharmaceutical design · 2013Trial
- 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
- Identification of novel NRF2-dependent genes as regulators of lead and arsenic toxicity in neural progenitor cells.Journal of hazardous materials · 2024Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Endothelial APC/PAR1 distinctly regulates cytokine-induced pro-inflammatory VCAM-1 expression.Frontiers in molecular biosciences · 2023Article
- Diversification of PAR signaling through receptor crosstalk.Cellular & molecular biology letters · 2022Review
- Protection of ischemic white matter and oligodendrocytes in mice by 3K3A-activated protein C.The Journal of experimental medicine · 2022Article
- 3K3A-Activated Protein C Protects the Blood-Brain Barrier and Neurons From Accelerated Ischemic Injury Caused by Pericyte Deficiency in Mice.Frontiers in neuroscience · 2022Article
- Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies.Experimental neurology · 2021Review
- Stroke Treatment With PAR-1 Agents to Decrease Hemorrhagic Transformation.Frontiers in neurology · 2021Review
- Phosphoproteomic analysis of protease-activated receptor-1 biased signaling reveals unique modulators of endothelial barrier function.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Next Step in the Treatment of Stroke.Frontiers in neurology · 2020Review
- Activated Protein C Attenuates Experimental Autoimmune Encephalomyelitis Progression by Enhancing Vascular Integrity and Suppressing Microglial Activation.Frontiers in neuroscience · 2020Article
- Neuroprotection and vasculoprotection using genetically targeted protease-ligands.Brain research · 2019Article
- Activated Protein C in Cutaneous Wound Healing: From Bench to Bedside.International journal of molecular sciences · 2019Review
- 3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice.The Journal of experimental medicine · 2019Article
- Synthesis and biological evaluation of 2,2-dimethylbenzopyran derivatives as potent neuroprotection agents.RSC advances · 2019Article
- Review
Corrections and comments
- Retraction · 2024-10-29Concerns/Issues about Data · Concerns/Issues about Image · Duplication of/in Image · Investigation by Journal/Publisher · Manipulation of Images · Objections by Author(s) · Original Data and/or Images not Provided and/or not Available ·
- Retracted
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The anticoagulant activated protein C (APC) protects neurons and endothelium via protease activated receptor (PAR)1, PAR3 and endothelial protein C receptor. APC is neuroprotective in stroke models. Bleeding complications may limit the pharmacologic utility of APC. Here, we compared the 3K3A-APC mutant with 80% reduced anticoagulant activity and wild-type (wt)-APC. Murine 3K3A-APC compared with wt-APC protected mouse cortical neurons from N-methyl-D-aspartate-induced apoptosis with twofold greater efficacy and more potently reduced N-methyl-D-aspartate excitotoxic lesions in vivo. Human 3K3A-APC protected human brain endothelial cells (BECs) from oxygen/glucose deprivation with 1.7-fold greater efficacy than wt-APC. 3K3A-APC neuronal protection required PAR1 and PAR3, as shown by using PAR-specific blocking antibodies and PAR1- and PAR3-deficient cells and mice. BEC protection required endothelial protein C receptor and PAR1. In neurons and BECs, 3K3A-APC blocked caspase-9 and -3 activation and induction of p53, and decreased the Bax/Bcl-2 pro-apoptotic ratio. After distal middle cerebral artery occlusion (dMCAO) in mice, murine 3K3A-APC compared with vehicle given 4:00 h after dMCAO improved the functional outcome and reduced the infarction volume by 50% within 3 days. 3K3A-APC compared with wt-APC multi-dosing therapy at 12:00 h, 1, 3, 5 and 7 days after dMCAO significantly improved functional recovery and reduced the infarction volume by 75% and 38%, respectively, within 7 days. The wt-APC, but not 3K3A-APC, significantly increased the risk of intracerebral bleeding as indicated by a 50% increase in hemoglobin levels in the ischemic hemisphere. Thus, 3K3A-APC offers a new approach for safer and more efficacious treatments of neurodegenerative disorders and stroke with APC.
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.