RAPID INDUCTION OF ALZHEIMER A-BETA AMYLOID FORMATION BY ZINC
RAPID INDUCTION OF ALZHEIMER A-BETA AMYLOID FORMATION BY ZINC
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DOI：
10.1126/science.8073293
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发表时间：
1994-09-02
期刊：
影响因子：
56.9
通讯作者：
TANZI, RE
中科院分区：
文献类型：
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作者：
BUSH, AI;PETTINGELL, WH;TANZI, RE
A β（1-40）是阿尔茨海默氏病脑淀粉样蛋白的主要成分，存在于脑脊液中，并在高浓度（小于或等于3.7 mM）下保持相对可溶。因此，诱导A β淀粉样蛋白形成的生理因素可以为该疾病的发病机制提供线索。已经表明，人A β特异性地和饱和地结合锌。在这里，浓度高于300 nM的锌迅速使人A β（1-40）溶液不稳定，诱导着色淀粉样蛋白形成。然而，大鼠A β（1-40）结合锌的热情较低，对这些影响具有免疫力，这可能解释了这些动物形成大脑A β淀粉样蛋白的稀缺性。这些数据表明大脑锌代谢在阿尔茨海默病的神经发病机制中发挥作用。
A beta(1-40), a major component of Alzheimer's disease cerebral amyloid, is present in the cerebrospinal fluid and remains relatively soluble at high concentrations (less than or equal to 3.7 mM). Thus, physiological factors which induce A beta amyloid formation could provide clues to the pathogenesis of the disease. It has been shown that human A beta specifically and saturably binds zinc. Here, concentrations of zinc above 300 nM rapidly destabilized human A beta(1-40) solutions, inducing tinctorial amyloid formation. However, rat A beta(1-40) binds zinc less avidly and is immune to these effects, perhaps explaining the scarcity with which these animals form cerebral A beta amyloid. These data suggest a role for cerebral zinc metabolism in the neuropathogenesis of Alzheimer's disease.