In vitro and in vivo degradation of Aβ peptide by peptidases coupled to erythrocytes
In vitro and in vivo degradation of Aβ peptide by peptidases coupled to erythrocytes
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DOI：
10.1016/j.peptides.2007.09.015
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发表时间：
2007-12-01
期刊：
影响因子：
3
通讯作者：
Hersh, Louis B.
中科院分区：
文献类型：
--
作者：
Liu, Yinxing;Guan, Hanjun;Hersh, Louis B.
一般认为，淀粉样蛋白P肽（A β）是阿尔茨海默病的关键介质。治疗性干预已被导向损害合成或加速A β的清除。血液和脑A β之间的平衡存在于通过运输A β穿过血脑屏障的载体介导下。被动免疫疗法已被证明在AD的小鼠模型中有效，其中血浆携带的抗体结合血浆A β，导致A β从脑中流出。作为被动免疫疗法的替代方案，我们已经考虑使用A β降解肽酶来降低血浆A β水平。在这里，我们比较了三种A β降解肽酶降解A β的能力。生物素化的肽酶通过链霉亲和素偶联到生物素化的红细胞表面。这些红细胞结合的肽酶降解血浆中的A β肽。因此，与红系细胞表面结合或在红系细胞表面上表达的肽酶代表了被动免疫疗法的替代方案。(c)2007年爱思唯尔公司All rights reserved.
It is generally believed that amyloid p peptides (A beta) are the key mediators of Alzheimer's disease. Therapeutic interventions have been directed toward impairing the synthesis or accelerating the clearance of A beta. An equilibrium between blood and brain A beta exists mediated by carriers that transport A beta across the blood-brain barrier. Passive immunotherapy has been shown to be effective in mouse models of AD, where the plasma borne antibody binds plasma A beta causing an efflux of A beta from the brain. As an alternative to passive immunotherapy we have considered the use of A beta-degrading peptidases to lower plasma A beta levels. Here we compare the ability of three A beta-degrading peptidases to degrade A beta. Biotinylated peptidases were coupled to the surface of biotinylated erythrocytes via streptavidin. These erythrocyte-bound peptidases degrade A beta peptide in plasma. Thus, peptidases bound to or expressed on the surface of erythroid cells represent an alternative to passive immunotherapy. (c) 2007 Elsevier Inc. All rights reserved.