ReviewFrontiers in cellular neuroscience2015
Tissue-type plasminogen activator is a neuroprotectant in the central nervous system.
Review in Frontiers in cellular neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Pooled it
- Tissue Plasminogen Activator as an Approved Strategy for Ischemic Stroke: A Review of tPA's Structure, Mechanism of Action and the Novel Targeting Methods.Journal of molecular neuroscience : MN · 2025Review
- Novel Roles for Urokinase- and Tissue-Type Plasminogen Activators in the Pathogenesis of Mood Disorders.International journal of molecular sciences · 2025Review
- New Wine in an Old Bottle: tPA for Ischemic Stroke Management.Translational stroke research · 2025Article
- Lactoferrin-derived peptide PXL01 impacts nerve regeneration after sciatic nerve reconstruction in healthy and diabetic rats.Frontiers in cell and developmental biology · 2025Article
- Multi-Omics Reveals Disrupted Immunometabolic Homeostasis and Oxidative Stress in Adipose Tissue of Dairy Cows with Subclinical Ketosis: A Sphingolipid-Centric Perspective.Antioxidants (Basel, Switzerland) · 2024Article
- An LRP1-binding motif in cellular prion protein replicates cell-signaling activities of the full-length protein.JCI insight · 2023Article
- Plasma biomarkers of endothelial function, inflammation and oxidative stress in individuals with non-freezing cold injury.Experimental physiology · 2023Article
- Recombinant Adenovirus-Mediated HIF-lα Ameliorates Neurological Dysfunction by Improving Energy Metabolism in Ischemic Penumbra After Cerebral Ischemia-Reperfusion in Rats.Neuropsychiatric disease and treatment · 2023Article
- SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock.Frontiers in physiology · 2023Review
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Ceramides as Mediators of Oxidative Stress and Inflammation in Cardiometabolic Disease.International journal of molecular sciences · 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 use of recombinant tissue plasminogen activator in in acute ischemic stroke is associated with increased level of BDNF.Journal of thrombosis and thrombolysis · 2021Article
- Plasminogen activator receptor assemblies in cell signaling, innate immunity, and inflammation.American journal of physiology. Cell physiology · 2021Review
- The plasminogen activating system in the pathogenesis of Alzheimer's disease.Neural regeneration research · 2021Review
- A soluble derivative of PrPThe Journal of biological chemistry · 2020Article
- Assessment of recombinant tissue plasminogen activator (rtPA) toxicity in cultured neural cells and subsequent treatment with poly-arginine peptide R18D.Neurochemical research · 2020Article
- Tissue-type plasminogen activator-primed human iPSC-derived neural progenitor cells promote motor recovery after severe spinal cord injury.Scientific reports · 2019Article
- The role of endogenous tissue-type plasminogen activator in neuronal survival after ischemic stroke: friend or foe?Cellular and molecular life sciences : CMLS · 2019Review
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Tissue-type plasminogen activator (tPA) is a serine proteinase found not only in the intravascular space but also in a well-defined sub-set of neurons in the brain. tPA is rapidly released from neurons after either exposure to hypoxia or hypoglycemia in vitro, or the induction of cerebral ischemia in vivo. It has been proposed that tPA has a neurotoxic effect in the ischemic brain. However, recent evidence indicate that once released into the synaptic cleft tPA activates specific cell signaling pathways that promote the detection and adaptation to metabolic stress. More specifically, the non-proteolytic interaction of tPA with N-methyl-D-aspartate receptors (NMDARs) and a member of the low-density lipoprotein receptor (LDLR) family in dendritic spines activates the mammalian target of rapamycin (mTOR) pathway that adapts cellular processes to the availability of energy and metabolic resources. TPA-induced mTOR activation in neurons leads to hypoxia-inducible factor 1α (HIF-1α) accumulation, HIF-1α-induced expression and membrane recruitment of the neuronal transporter of glucose GLUT3, and GLUT3-mediated uptake of glucose. These and other data discussed in this Review suggest that the postulated neurotoxic effect of tPA needs to be reconsidered and instead indicate the emergence of a new paradigm: that tPA is an endogenous neuroprotectant in the central nervous system (CNS).
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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.