Real-time and single fibril observation of the formation of amyloid β spherulitic structures
Real-time and single fibril observation of the formation of amyloid β spherulitic structures
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DOI：
10.1074/jbc.m606072200
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发表时间：
2006-11-03
影响因子：
4.8
通讯作者：
Goto, Yuji
中科院分区：
文献类型：
--
作者：
Ban, Tadato;Morigaki, Kenichi;Goto, Yuji
在阿尔茨海默病中，淀粉样蛋白β，一种由大的淀粉样蛋白前体蛋白裂解产生的39-43个残基的肽，经历构象变化以形成淀粉样蛋白原纤维并作为老年淀粉样蛋白斑沉积在脑的细胞外大脑皮质中。然而，内在的线性淀粉样纤维如何形成球形老年斑的机制是未知的。与全内反射荧光显微镜结合使用硫磺素T，淀粉样蛋白特异性荧光染料，我们成功地观察到形成的老年斑块状球晶结构的直径约为15 μ m的化学改性的石英表面。在单个原纤维水平的实时观察显示，在没有与表面紧密接触的情况下，淀粉样蛋白原纤维从核心的协同和径向生长导致巨大的球晶结构。这些结果提示了老年斑形成的潜在物理化学机制，对于预防阿尔茨海默病至关重要。
In Alzheimer disease, amyloid beta, a 39-43-residue peptide produced by cleavage from a large amyloid precursor protein, undergoes conformational change to form amyloid fibrils and deposits as senile amyloid plaques in the extracellular cerebral cortices of the brain. However, the mechanism of how the intrinsically linear amyloid fibrils form spherical senile plaques is unknown. With total internal reflection fluorescence microscopy combined with the use of thioflavin T, an amyloid-specific fluorescence dye, we succeeded in observing the formation of the senile plaque-like spherulitic structures with diameters of around 15 mu m on the chemically modified quartz surface. Real-time observation at a single fibrillar level revealed that, in the absence of tight contact with the surface, the cooperative and radial growth of amyloid fibrils from the core leads to a huge spherulitic structure. The results suggest the underlying physicochemical mechanism of senile plaque formation, essential for obtaining insight into prevention of Alzheimer disease.