Gupta-Bansal R, Brunden K R
Exploratory Research Group, Gliatech Inc., Cleveland, Ohio 44122, USA.
J Neurochem. 1998 Jan;70(1):292-8. doi: 10.1046/j.1471-4159.1998.70010292.x.
Various data suggest that Alzheimer's disease results from the accumulation of amyloid beta (A beta) peptide fibrils and the consequent formation of senile plaques in the cognitive regions of the brain. One approach to lowering senile plaque burden in Alzheimer's disease brain is to identify compounds that will increase the degradation of existing amyloid fibrils. Previous studies have shown that proteoglycans and serum amyloid P (SAP), molecules that localize to senile plaques, bind to A beta fibrils and protect the amyloid peptide from proteolytic breakdown. Therefore, molecules that prevent the binding of SAP and/or proteoglycans to fibrillar A beta might increase plaque degradation and prove useful in the treatment of Alzheimer's disease. The nature of SAP and proteoglycan binding to A beta is defined further in the present study. SAP binds to both fibrillar and nonfibrillar forms of A beta. However, only the former is rendered resistant to proteolysis after SAP association. It is interesting that both SAP and proteoglycan binding to A beta fibrils can be inhibited by glycosaminoglycans and Congo red. Unexpectedly, Congo red protects fibrillar A beta from breakdown, suggesting that this compound and other structurally related molecules are unlikely to be suitable for use in the treatment of Alzheimer's disease.
各种数据表明，阿尔茨海默病是由淀粉样β（Aβ）肽原纤维的积累以及随后在大脑认知区域形成老年斑所致。降低阿尔茨海默病大脑中老年斑负担的一种方法是鉴定能够增加现有淀粉样原纤维降解的化合物。先前的研究表明，定位在老年斑中的蛋白聚糖和血清淀粉样蛋白P（SAP）与Aβ原纤维结合，并保护淀粉样肽免受蛋白水解降解。因此，阻止SAP和/或蛋白聚糖与纤维状Aβ结合的分子可能会增加斑块降解，并被证明对治疗阿尔茨海默病有用。本研究进一步确定了SAP和蛋白聚糖与Aβ结合的性质。SAP与纤维状和非纤维状形式的Aβ都结合。然而，只有前者在与SAP结合后才对蛋白水解具有抗性。有趣的是，糖胺聚糖和刚果红都能抑制SAP和蛋白聚糖与Aβ原纤维的结合。出乎意料的是，刚果红保护纤维状Aβ不被分解，这表明该化合物和其他结构相关分子不太可能适用于治疗阿尔茨海默病。
