A pilot proteomic study of amyloid precursor interactors in Alzheimer's disease

A pilot proteomic study of amyloid precursor interactors in Alzheimer's disease
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DOI:
10.1002/ana.20554
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发表时间:
2005-08-01
影响因子:
11.2
通讯作者:
Bredesen, DE
Bredesen, DE
中科院分区:
医学1区
文献类型:
--
作者:
Cottrell, BA;Galvan, V;Bredesen, DE

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已经使用了几种方法来鉴定与β-淀粉样前体蛋白(APP)相互作用的蛋白质。然而,很少有研究涉及阿尔茨海默病患者脑组织中与APP相关的蛋白质的鉴定。我们报告的结果进行了试点蛋白质组学研究的复合物与APP在阿尔茨海默病患者和正常对照组的大脑样本的免疫沉淀。鉴定的21种蛋白质可分为5个功能类别:分子伴侣、细胞骨架和结构蛋白、参与运输的蛋白质、衔接子和酶。在鉴定的蛋白质中,有六种以前曾被报道为直接、间接或遗传推断的APP相互作用物。与APP免疫沉淀的其他15个蛋白质是新的潜在伙伴。我们证实了APP相互作用的Western印迹和coimmunolocalization在脑组织中,为5的21个interactors。与以前的研究一致,我们的研究结果是兼容的参与APP轴突运输和囊泡跟踪,并与潜在的协会APP与细胞蛋白质折叠/蛋白质降解系统。
Several approaches have been used in an effort to identify proteins that interact with beta-amyloid precursor protein (APP). However, few studies have addressed the identification of proteins associated with APP in brain tissue from patients with Alzheimer's disease. We report the results of a pilot proteomic study performed on complexes immunoprecipitated with APP in brain samples of patients with Alzheimer's disease and normal control subjects. The 21 proteins identified could be grouped into five functional classes: molecular chaperones, cytoskeletal and structural proteins, proteins involved in trafficking, adaptors, and enzymes. Among the proteins identified, six had been reported previously as direct, indirect, or genetically inferred APP interactors. The other 15 proteins immunoprecipitated with APP were novel potential partners. We confirmed the APP interaction by Western blotting and coimmunolocalization in brain tissues, for 5 of the 21 interactors. In agreement with previous studies, our results are compatible with an involvement of APP in axonal transport and vesicular tracking, and with a potential association of APP with cellular protein folding/protein degradation systems.