The Tissue Plasminogen Activator-Plasminogen Proteolytic Cascade Accelerates Amyloid-β (Aβ) Degradation and Inhibits Aβ-Induced Neurodegeneration
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Accumulation of the amyloid-β (Aβ) peptide depends on both its generation and clearance. To better define clearance pathways, we have evaluated the role of the tissue plasminogen activator (tPA)-plasmin system in Aβ degradationin vivo. In two different mouse models of Alzheimer's disease, chronically elevated Aβ peptide in the brain correlates with the upregulation of plasminogen activator inhibitor-1 (PAI-1) and inhibition of the tPA-plasmin system. In addition, Aβ injected into the hippocampus of mice lacking either tPA or plasminogen persists, inducing PAI-1 expression and causing activation of microglial cells and neuronal damage. Conversely, Aβ injected into wild-type mice is rapidly cleared and does not cause neuronal degeneration. Thus, the tPA-plasmin proteolytic cascade aids in the clearance of Aβ, and reduced activity of this system may contribute to the progression of Alzheimer's disease.
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Tissue plasminogen activator (tPA) is required for acute stress to activate indices of structural plasticity and to enhance anxiety in the amygdala.
“in that tissue plasminogen activator (tPA) is required for acute stress to activate not only indices of structural plasticity but also to enhance anxiety (Melchor et al., 2003)”
From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as Melchor et al., 2003
In the amygdala, tPA is required for acute stress to activate indices of structural plasticity and to enhance anxiety.
“Nevertheless, in the amygdala, there is some evidence regarding mechanism, in that tPA is required for acute stress to activate not only indices of structural plasticity but also to enhance anxiety.97”
From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [97]
Acute stress induces spine synapses in the CA1 region of hippocampus, and both acute and chronic stress increase spine synapse formation in amygdala, but chronic stress decreases it in hippocampus.
“Acute stress induces spine synapses in the CA1 region of hippocampus98 and both acute and chronic stress also increases spine synapse formation in amygdala,95-99 but chronic stress decreases it in hippocampus.77”
From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [97]
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References 33 · Cited by 202
- Authors
- Melchor, J. P., Pawlak, R., & Strickland, S.
- Affiliations
- Rockefeller University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-10-01
- Volume
- 23
- Issue
- 26
- Pages
- 8867-8871
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W4321317599
- Cited by
- 202
- References
- 33
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 12 · 2022: 10 · 2021: 9 · 2020: 12 · 2019: 5 · 2018: 9 · 2017: 8 · 2016: 5 · 2015: 5 · 2014: 4 · 2013: 9 · 2012: 6
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- tissue plasminogen activator, plasminogen, plasminogen activator inhibitor-1, amyloid-beta clearance, amyloid beta degradation, Alzheimer's disease, neurodegeneration, microglial activation, hippocampus, proteolytic cascade
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