ArticleProceedings of the National Academy of Sciences of the United States of America2008
Enhanced clearance of Abeta in brain by sustaining the plasmin proteolysis cascade.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 140 citations in OpenAlex.
- A contemporary review of plasminogen activator inhibitor 1 in cardiovascular disease and broader disease state implications.Blood vessels, thrombosis & hemostasis · 2026Review
- Review
- The Double-Edged Sword Effect of the Fibrinolytic System in Alzheimer's Disease.Cellular and molecular neurobiology · 2026Review
- Rather a versatile multi-tool than a sword: an integral role of the plasminogen system in health and disease.Frontiers in immunology · 2026Review
- Bridging the barrier: insights into blood biomarkers and therapeutic strategies targeting choroid plexus and BBB dysfunction in alzheimer's disease.Biomarker research · 2025Review
- Molecular Evidence for Altered Angiogenesis in Neuroinflammation-Associated Schizophrenia and Bipolar Disorder Implicate an Abnormal Midbrain Blood-Brain Barrier.Schizophrenia bulletin · 2025Article
- Elevated cerebrospinal fluid levels of SERPIN E1 in participants with lewy body diseases.NPJ Parkinson's disease · 2025Article
- The neurobiological foundation of effective repetitive transcranial magnetic brain stimulation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Probing Macromolecular Interactions by Loss of Solvent Content in Protein Crystals: Application to the Amyloid‑β Peptide Binding to Transthyretin.Crystal growth & design · 2025Article
- Article
- Neuro-Adipokine Crosstalk in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- The probable role of tissue plasminogen activator/neuroserpin axis in Alzheimer's disease: a new perspective.Acta neurologica Belgica · 2024Review
- 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
- Crosstalk between small-cell lung cancer cells and astrocytes mimics brain development to promote brain metastasis.Nature cell biology · 2023Article
- Advances in Amyloid-β Clearance in the Brain and Periphery: Implications for Neurodegenerative Diseases.Experimental neurobiology · 2023Review
- Aging, Plasminogen Activator Inhibitor 1, Brain Cell Senescence, and Alzheimer's Disease.Aging and disease · 2023Article
- Modulations of the neuronal trafficking of tissue-type plasminogen activator (tPA) influences glutamate release.Cell death & disease · 2023Article
- Alzheimer's Disease Severity Is Associated with an Imbalance in Serum Levels of Enzymes Regulating Plasmin Synthesis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Contribution of proteases to the hallmarks of aging and to age-related neurodegeneration.Aging cell · 2022Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amyloid hypothesis states that a variety of neurotoxic beta-amyloid (Abeta) species contribute to the pathogenesis of Alzheimer's disease. Accordingly, a key determinant of disease onset and progression is the appropriate balance between Abeta production and clearance. Enzymes responsible for the degradation of Abeta are not well understood, and, thus far, it has not been possible to enhance Abeta catabolism by pharmacological manipulation. We provide evidence that Abeta catabolism is increased after inhibition of plasminogen activator inhibitor-1 (PAI-1) and may constitute a viable therapeutic approach for lowering brain Abeta levels. PAI-1 inhibits the activity of tissue plasminogen activator (tPA), an enzyme that cleaves plasminogen to generate plasmin, a protease that degrades Abeta oligomers and monomers. Because tPA, plasminogen and PAI-1 are expressed in the brain, we tested the hypothesis that inhibitors of PAI-1 will enhance the proteolytic clearance of brain Abeta. Our data demonstrate that PAI-1 inhibitors augment the activity of tPA and plasmin in hippocampus, significantly lower plasma and brain Abeta levels, restore long-term potentiation deficits in hippocampal slices from transgenic Abeta-producing mice, and reverse cognitive deficits in these mice.
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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.