TY - JOUR
T1 - Urokinase-type plasminogen activator inhibits amyloid-β neurotoxicity and fibrillogenesis via plasminogen
AU - Tucker, H. Michael
AU - Kihiko-Ehmann, Muthoni
AU - Estus, Steven
PY - 2002/10/15
Y1 - 2002/10/15
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Plasmin
KW - Proteolysis
KW - uPA
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U2 - 10.1002/jnr.10417
DO - 10.1002/jnr.10417
M3 - Article
C2 - 12271474
AN - SCOPUS:0037107974
SN - 0360-4012
VL - 70
SP - 249
EP - 255
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 2
ER -