Urokinase-type plasminogen activator inhibits amyloid-? neurotoxicity and fibrillogenesis via plasminogen
| Autor: | H. Michael Tucker, Muthoni Kihiko-Ehmann, Steven Estus |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cell Survival
Macromolecular Substances Plasmin Proteolysis Fluorescent Antibody Technique Cellular and Molecular Neuroscience Alzheimer Disease In vivo mental disorders medicine Animals Humans Cells Cultured Neurons Urokinase Amyloid beta-Peptides medicine.diagnostic_test Chromosomes Human Pair 10 Chemistry Neurotoxicity Plasminogen Fibrillogenesis medicine.disease Urokinase-Type Plasminogen Activator Molecular biology In vitro Rats nervous system diseases Microscopy Electron Drug Therapy Combination Plasminogen activator Protein Binding medicine.drug |
| Zdroj: | Journal of Neuroscience Research. 70:249-255 |
| ISSN: | 1097-4547 0360-4012 |
| DOI: | 10.1002/jnr.10417 |
| Popis: | Amyloid-beta (Abeta) appears central to Alzheimer's disease (AD), aggregates spontaneously, and is neurotoxic to neurons in vitro. Recently, several groups reported a familial AD locus on chromosome 10. Here, we note that urokinase-type plasminogen activator (uPA) is located within this locus. Previously, we reported that uPA and its functional homolog, tissue-type plasminogen activator, are induced by Abeta treatment of neurons in vitro as well as in a mouse model of Abeta accumulation in vivo. Moreover, the target of plasminogen activators, plasmin, degraded nonaggregated and aggregated Abeta and modulated Abeta toxicity and deposition. Here, we have evaluated the effects of uPA and plasminogen on Abeta fibril formation and neurotoxicity. We report that the combination of uPA and plasminogen, but neither alone, inhibits Abeta toxicity, reduces Abeta deposition in vitro, and inhibits Abeta fibrillogenesis. We interpret these observations as suggesting that uPA represents a possible candidate gene for the chromosome 10 familial AD locus. |
| Databáze: | OpenAIRE |
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