ARRESTING AMYLOIDOSIS IN-VIVO USING SMALL-MOLECULE ANIONIC SULFONATES OR SULFATES - IMPLICATIONS FOR ALZHEIMERS-DISEASE
ARRESTING AMYLOIDOSIS IN-VIVO USING SMALL-MOLECULE ANIONIC SULFONATES OR SULFATES - IMPLICATIONS FOR ALZHEIMERS-DISEASE
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DOI：
10.1038/nm0295-143
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发表时间：
1995-02-01
期刊：
影响因子：
82.9
通讯作者：
SZAREK, WA
中科院分区：
文献类型：
--
作者：
KISILEVSKY, R;LEMIEUX, LJ;SZAREK, WA
淀粉样蛋白是细胞外蛋白原纤维沉积物的术语，具有特征性的色调和结构特性。硫酸乙酰肝素或硫酸乙酰肝素蛋白多糖已在所有淀粉样蛋白中被发现，并与炎症相关 (AA) 淀粉样蛋白诱导的最早阶段有关。硫酸乙酰肝素与 AA 淀粉样蛋白前体和阿尔茨海默病淀粉样蛋白的 β 肽相互作用，赋予特有的二级和三级淀粉样蛋白结构特征。这些观察结果表明，干扰这种相互作用的分子可能会阻止或阻止淀粉样蛋白生成。我们合成了低分子量（135-1,000）阴离子磺酸盐或硫酸盐化合物。当口服给药时，这些化合物显着减少了小鼠脾脏 AA 淀粉样蛋白的进展。它们还在体外干扰硫酸乙酰肝素刺激的β-肽原纤维聚集。
Amyloid is a term for extracellular protein fibril deposits that have characteristic tinctorial and structural properties. Heparan sulphate, or the heparan sulphate proteoglycan perlecan, has been identified in all amyloids and implicated in the earliest stages of inflammation-associated (AA) amyloid induction. Heparan sulphate interacts with the AA amyloid precursor and the beta-peptide of Alzheimer's amyloid, imparting characteristic secondary and tertiary amyloid structural features. These observations suggest that molecules that interfere with this interaction may prevent or arrest amyloidogenesis. We synthesized low-molecular-weight (135-1,000) anionic sulphonate or sulphate compounds. When administered orally, these compounds substantially reduced murine splenic AA amyloid progression. They also interfered with heparan sulphate-stimulated beta-peptide fibril aggregation in vitro.