Cottrell Barbara A, Galvan Veronica, Banwait Surita, Gorostiza Olivia, Lombardo Christian R, Williams Tristan, Schilling Birgit, Peel Alyson, Gibson Bradford, Koo Edward H, Link Christopher D, Bredesen Dale E
Buck Institute for Age Research, Novato, CA 94945, USA.
Ann Neurol. 2005 Aug;58(2):277-89. doi: 10.1002/ana.20554.
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 trafficking, and with a potential association of APP with cellular protein folding/protein degradation systems.
为了鉴定与β淀粉样前体蛋白（APP）相互作用的蛋白质，人们采用了多种方法。然而，很少有研究涉及在阿尔茨海默病患者脑组织中鉴定与APP相关的蛋白质。我们报告了一项初步蛋白质组学研究的结果，该研究对阿尔茨海默病患者和正常对照受试者脑样本中用APP免疫沉淀的复合物进行了检测。鉴定出的21种蛋白质可分为五个功能类别：分子伴侣、细胞骨架和结构蛋白、参与运输的蛋白质、衔接蛋白和酶。在鉴定出的蛋白质中，有六种先前已被报道为直接、间接或基因推断的APP相互作用蛋白。与APP一起免疫沉淀的其他15种蛋白质是新的潜在伙伴。我们通过蛋白质印迹法和脑组织中的共免疫定位，对21种相互作用蛋白中的5种进行了APP相互作用的确认。与先前的研究一致，我们的结果表明APP参与轴突运输和囊泡运输，并可能与细胞蛋白质折叠/蛋白质降解系统相关。
