Dotti Carlos G, Galvan Cristian, Ledesma Maria Dolores
Cavalieri Ottolenghi Scientific Institute, Fondazione Cavalieri Ottolenghi, Università degli Studi di Torino, AO San Luigi Gonzaga, Orbassano, Italy.
Neurodegener Dis. 2004;1(4-5):205-12. doi: 10.1159/000080987.
Substantial recent evidence suggests that defects in amyloid peptide degradation can be at the base of cases of sporadic Alzheimer's disease (AD). Among the discovered brain enzymes with the capacity to degrade amyloid peptide, the serine protease plasmin acquires special physiological relevance because of its low levels in areas of AD human brains with a high susceptibility to amyloid plaque accumulation. In this article we comment on a series of observations supporting the fact that plasmin paucity in the brain is not simply a secondary event in the disease but rather a primary defect in certain cases of sporadic AD. We also refer to recent data pointing to alterations in raft membrane domains and diminished membrane cholesterol as the underlying cause. Finally, we discuss the possibility that plasmin deficiency in the brain could lead to AD symptomatology because of amyloid aggregation and the triggering of cell death signaling cascades.
最近大量证据表明，淀粉样肽降解缺陷可能是散发性阿尔茨海默病（AD）病例的病因。在已发现的具有降解淀粉样肽能力的脑酶中，丝氨酸蛋白酶纤溶酶具有特殊的生理意义，因为在对淀粉样斑块积累高度敏感的AD患者脑区中其水平较低。在本文中，我们对一系列观察结果进行评论，这些观察结果支持这样一个事实，即脑中纤溶酶缺乏并非该疾病的简单继发性事件，而是某些散发性AD病例的原发性缺陷。我们还提及了最近的数据，这些数据表明筏膜结构域的改变和膜胆固醇减少是其潜在原因。最后，我们讨论了脑内纤溶酶缺乏可能由于淀粉样蛋白聚集和细胞死亡信号级联反应的触发而导致AD症状的可能性。
