| First Author | Bi Oh S | Year | 2015 |
| Journal | Brain Res | Volume | 1597 |
| Pages | 159-67 | PubMed ID | 25454795 |
| Mgi Jnum | J:220906 | Mgi Id | MGI:5637452 |
| Doi | 10.1016/j.brainres.2014.11.042 | Citation | Bi Oh S, et al. (2015) Impacts of aging and amyloid-beta deposition on plasminogen activators and plasminogen activator inhibitor-1 in the Tg2576 mouse model of Alzheimer's disease. Brain Res 1597:159-67 |
| abstractText | Plasminogen activators (PAs), which convert plasminogen into the fibrinolytic protease plasmin, may initiate the degradation of amyloid-beta (Abeta) to suppress the amyloid pathogenesis. In that way, tissue plasminogen activator (tPA)-mediated plasmin activation could maintain a low level of Abeta deposition to delay the pathogenesis of Alzheimer's disease (AD). In a previous study, we reported that tPA/plasmin proteolytic activity is attenuated throughout the brain during aging or with Abeta accumulation but clustered intense around the amyloid plaques in AD brain. The present study demonstrates that the altered proteolytic activity primarily results from the competition between the expressions of tPA and plasminogen activator inhibitor-1 (PAI-1) in the brains of Tg2576 Abeta-transgenic mice, as revealed by immunohistochemistry and immunoblot assays. Compared with that in the brains of younger Tg2576 mice, tPA protein is generally reduced throughout the brain in older Tg2576 mice but elevated near amyloid plaques. In contrary, PAI-1 expression increases during aging or Abeta deposition with its clusters surrounding amyloid plaques. No significant alteration in the expression of urokinase plasminogen activator (uPA) is detected. These results suggest reciprocal feedback influences between tPA, PAI-1 and Abeta during aging and amyloid pathogenesis in AD brain; tPA-mediated plasmin activity is declined throughout the brain causing Abeta deposition during aging, and the Abeta deposits locally attract the cluster of tPA and/or PAI-1 around their deposits to competitively determine tPA/plasmin-mediated Abeta proteolysis. |
