Ledesma M D, Da Silva J S, Crassaerts K, Delacourte A, De Strooper B, Dotti C G
Cell Biology and Biophysics Program, EMBL, Heidelberg, Germany.
EMBO Rep. 2000 Dec;1(6):530-5. doi: 10.1093/embo-reports/kvd107.
The proteolytic processing of amyloid precursor protein (APP) has been linked to sphingolipid-cholesterol microdomains (rafts). However, the raft proteases that may be involved in APP cleavage have not yet been identified. In this work we present evidence that the protease plasmin is restricted to rafts of cultured hippocampal neurons. We also show that plasmin increases the processing of human APP preferentially at the alpha-cleavage site, and efficiently degrades secreted amyloidogenic and non-amyloidogenic APP fragments. These results suggest that brain plasmin plays a preventive role in APP amyloidogenesis. Consistently, we show that brain tissue from Alzheimer's disease patients contains reduced levels of plasmin, implying that plasmin downregulation may cause amyloid plaque deposition accompanying sporadic Alzheimer's disease.
淀粉样前体蛋白（APP）的蛋白水解加工与鞘脂 - 胆固醇微结构域（脂筏）有关。然而，可能参与APP切割的脂筏蛋白酶尚未被鉴定出来。在这项研究中，我们提供证据表明蛋白酶纤溶酶局限于培养的海马神经元的脂筏中。我们还表明，纤溶酶优先增加人APP在α-切割位点的加工，并有效降解分泌的淀粉样生成和非淀粉样生成的APP片段。这些结果表明，脑纤溶酶在APP淀粉样变过程中起预防作用。一致地，我们表明阿尔茨海默病患者的脑组织中纤溶酶水平降低，这意味着纤溶酶下调可能导致散发性阿尔茨海默病伴随的淀粉样斑块沉积。
