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Urokinase‐type plasminogen activator inhibits amyloid‐β neurotoxicity and fibrillogenesis via plasminogen
Author(s) -
Tucker H. Michael,
KihikoEhmann Muthoni,
Estus Steven
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10417
Subject(s) - fibrillogenesis , plasminogen activator , neurotoxicity , plasmin , chemistry , urokinase , in vitro , locus (genetics) , in vivo , tissue plasminogen activator , microbiology and biotechnology , biochemistry , biology , gene , endocrinology , toxicity , genetics , enzyme , organic chemistry
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. © 2002 Wiley‐Liss, Inc.