ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2000
The plasmin system is induced by and degrades amyloid-beta aggregates.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 2 of them syntheses 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.
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Who cites it
123 citing papers in PubMed, 2 syntheses or guidelines pooled it, 301 citations in OpenAlex.
- Pooled it
- Meta-analysis of the association between urokinase-plasminogen activator gene rs2227564 polymorphism and Alzheimer's disease.American journal of Alzheimer's disease and other dementias · 2013Pooled it
- Molecular Pathogenesis of Cerebral Amyloid Angiopathy in Alzheimer's Disease: The Role of the Central Fibrinolytic Cascade at the Neurovascular Unit.Molecular neurobiology · 2026Review
- Combating ageing beyond the cell: Emerging roles of extracellular proteostasis.The FEBS journal · 2026Review
- The Double-Edged Sword Effect of the Fibrinolytic System in Alzheimer's Disease.Cellular and molecular neurobiology · 2026Review
- The Role of Thyroid Hormones in Neurodegenerative Disorders: Opportunities and Challenges.Molecular neurobiology · 2025Review
- Article
- Article
- Shared interactions of six neurotropic viruses with 38 human proteins: a computational and literature-based exploration of viral interactions and hijacking of human proteins in neuropsychiatric disorders.Discover mental health · 2025Article
- Amyloid-beta metabolism in age-related neurocardiovascular diseases.European heart journal · 2025Review
- Exploring SERPINA3 as a neuroinflammatory modulator in Alzheimer's disease with sex and regional brain variations.Metabolic brain disease · 2025Article
- Amyloid and collagen templates in aortic valve calcification.Trends in molecular medicine · 2024Article
- The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer's Disease Etiopathology.Antioxidants (Basel, Switzerland) · 2024Review
- Article
- Histone acetylation in an Alzheimer's disease cell model promotes homeostatic amyloid-reducing pathways.Acta neuropathologica communications · 2024Article
- The effect of epigenetic aging on neurodegenerative diseases: a Mendelian randomization study.Frontiers in endocrinology · 2024Article
- Pharmacological inhibition of plasminogen activator inhibitor-1 prevents memory deficits and reduces neuropathology in APP/PS1 mice.Psychopharmacology · 2023Article
- Tranexamic acid for haemostasis and beyond: does dose matter?Thrombosis journal · 2023Review
- Advances in Amyloid-β Clearance in the Brain and Periphery: Implications for Neurodegenerative Diseases.Experimental neurobiology · 2023Review
- Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy.Pharmaceutics · 2023Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Amyloid-beta (Abeta) appears critical to Alzheimer's disease. To clarify possible mechanisms of Abeta action, we have quantified Abeta-induced gene expression in vitro by using Abeta-treated primary cortical neuronal cultures and in vivo by using mice transgenic for the Abeta precursor (AbetaP). Here, we report that aggregated, but not nonaggregated, Abeta increases the level of the mRNAs encoding tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Moreover, tPA and uPA were also upregulated in aged AbetaP overexpressing mice. Because others have reported that Abeta aggregates can substitute for fibrin aggregates in activating tPA post-translationally, the result of tPA induction by Abeta would be cleavage of plasminogen to the active protease plasmin. To gain insights into the possible actions of plasmin, we evaluated the hypotheses that tPA and plasmin may mediate Abeta in vitro toxicity or, alternatively, that plasmin activation may lead to Abeta degradation. In evaluating these conflicting hypotheses, we found that purified plasmin degrades Abeta with physiologically relevant efficiency, i.e., approximately 1/10th the rate of plasmin on fibrin. Mass spectral analyses show that plasmin cleaves Abeta at multiple sites. Electron microscopy confirms indirect assays suggesting that plasmin degrades Abeta fibrils. Moreover, exogenously added plasmin blocks Abeta neurotoxicity. In summation, we interpret these results as consistent with the possibility that the plasmin pathway is induced by aggregated Abeta, which can lead to Abeta degradation and inhibition of Abeta actions.
Indexed as
Identifiers
10818128PMC6772619W2164672119What 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.