Brain Amyloid — A Physicochemical Perspective
Brain Amyloid — A Physicochemical Perspective
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DOI：
10.1111/j.1750-3639.1996.tb00797.x
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发表时间：
1996-04
期刊：
影响因子：
6.4
通讯作者：
J. Maggie;P. Mantyh
中科院分区：
文献类型：
--
作者：
J. Maggie;P. Mantyh
形成稳定的交叉β原纤维的能力是人β淀粉样肽（Aβ）的固有理化特性，A β形成阿尔茨海默病（AD）的脑淀粉样蛋白。这种疏水性=40-mer的高淀粉样变性和低溶解度在过去一直是其研究的障碍，但近年来合成肽和新物理方法的可用性使许多新方法成为可能。Aβ聚集（与初始病灶形成相关）和Aβ沉积（与斑块生长和成熟相关！体外研究已经允许定量地探索结构/活性关系和动力学，并确定这些过程在生物化学上是不同的。在血管和实质淀粉样蛋白中发现了具有不同物理化学特性的不同形式的肽。各种光谱方法已被用于探索Aβ在溶液和固相中的三维构象，并证明该肽在每种状态下采用不同的构型。Aβ从溶液到纤维的转化需要一个重要的构象转变。这些观察结果提示了治疗AD的新的治疗靶点。
The ability to form stable cross‐β fibrils is an intrinsic physicochemical characteristic of the human β‐amyloid peptide (Aβ), which forms the brain amyloid of Alzheimer's disease (AD). The high amyloidogenicity and low solubility of this hydrophobic =40‐mer have been barriers to its study in the past, but the availability of synthetic peptide and new physical methods has enabled many novel approaches in recent years. Model systems for Aβ aggregation (relevant to initial nidus formation) and Aβ deposition (relevant to plaque growth and maturation! in vitro have allowed structure/activity relationships and kinetics to be explored quantitatively, and established that these processes' are biochemically distinct. Different forms of the peptide, with different physicochemical characteristics, are found in vascular and parenchymal amyloid. Various spectroscopic methods have been used to explore the three‐dimensional conformation of Aβ both in solution and in solid phase, and demonstrated that the peptide adopts a different configuration in each state. A significant conformational transition is essential to the transformation of Aβ from solution to fibril. These observations suggest new therapeutic targets for the treatment of AD.