Urokinase-type plasminogen activator inhibits amyloid-β neurotoxicity and fibrillogenesis via plasminogen

H. Michael Tucker, Muthoni Kihiko-Ehmann, Steven Estus

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Amyloid-β (Aβ) 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 Aβ treatment of neurons in vitro as well as in a mouse model of Aβ accumulation in vivo. Moreover, the target of plasminogen activators, plasmin, degraded nonaggregated and aggregated Aβ and modulated Aβ toxicity and deposition. Here, we have evaluated the effects of uPA and plasminogen on Aβ fibril formation and neurotoxicity. We report that the combination of uPA and plasminogen, but neither alone, inhibits Aβ toxicity, reduces Aβ deposition in vitro, and inhibits Aβ fibrillogenesis. We interpret these observations as suggesting that uPA represents a possible candidate gene for the chromosome 10 familial AD locus.

Original languageEnglish
Pages (from-to)249-255
Number of pages7
JournalJournal of Neuroscience Research
Issue number2
StatePublished - Oct 15 2002


  • Alzheimer's disease
  • Plasmin
  • Proteolysis
  • uPA

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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