Neuronal Death in the Hippocampus Is Promoted by Plasmin-Catalyzed Degradation of Laminin
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Excess excitatory amino acids can provoke neuronal death in the hippocampus, and the extracellular proteases tissue plasminogen activator (tPA) and plasmin (ogen) have been implicated in this death. To investigate substrates for plasmin that might influence neuronal degeneration, extracellular matrix (ECM) protein expression was examined. Laminin is expressed in the hippocampus and disappears after excitotoxin injection. Laminin disappearance precedes neuronal death, is spatially coincident with regions that exhibit neuronal loss, and is blocked by either tPA-deficiency or infusion of a plasmin inhibitor, both of which also block neuronal degeneration. Preventing neuron-laminin interaction by infusion of anti-laminin antibodies into tPA-deficient mice restores excitotoxic sensitivity to their hippocampal neurons. These results indicate that disruption of neuron-ECM interaction via tPA/plasmin catalyzed degradation of laminin sensitizes hippocampal neurons to cell death.
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Compromised blood-brain barrier integrity permits the direct entry of neurotoxic thrombin and plasmin, leading to synapse loss.
“Compromised blood–brain barrier integrity permits the direct entry of neurotoxic thrombin and plasmin, leading to synapse loss (41, 42).”
From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [42]
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- Authors
- Chen, Z.-L., & Strickland, S.
- Affiliations
- Stony Brook University (US)
- Corresponding author
- Strickland, Sidney
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1997-12
- Volume
- 91
- Issue
- 7
- Pages
- 917-925
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2086386772
- Cited by
- 632
- References
- 47
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 16 · 2019: 5 · 2018: 10 · 2017: 11 · 2016: 12 · 2015: 11 · 2014: 12 · 2013: 17 · 2012: 16
- FWCI
- 12.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS035704, NS35704)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- neuronal cell death, hippocampus, laminin, plasmin, tissue plasminogen activator, excitotoxicity, extracellular matrix, excitatory amino acids, plasmin inhibitor, anti-laminin antibodies
- MeSH terms
- Animals, Catalysis, Fibrinolysin, Hippocampus, Kainic Acid, Laminin, Male, Neurons, Neurotoxins, Tissue Plasminogen Activator, Cell Death, Excitatory Amino Acid Agonists, Mice
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