Zhong Z, Quon D, Higgins L S, Higaki J, Cordell B
Scios Nova Inc., Mountain View, California 94043.
J Biol Chem. 1994 Apr 22;269(16):12179-84.
The 4-kDa beta-amyloid protein that forms fibrillar deposits in Alzheimer's diseased brains is derived from a large precursor, the beta-amyloid precursor protein (beta-APP). Recently, it has been reported that beta-amyloid is normally produced and secreted by cultured mammalian cells. In our studies involving recombinant expression of beta-APP, increased yields of beta-amyloid were associated with expression of aberrant beta-APP molecules. Deletion mutations within the beta-amyloid domain, incorrect beta-APP isoform expression in fibroblasts or neuronal cells, or excess amounts of beta-APP all led to increases in beta-amyloid production. Aberrant beta-APP appears to be diverted from the secretory pathway and then degraded to beta-amyloid.
在阿尔茨海默病患者大脑中形成纤维状沉积物的4千道尔顿β-淀粉样蛋白源自一种大型前体蛋白，即β-淀粉样前体蛋白（β-APP）。最近有报道称，β-淀粉样蛋白通常由培养的哺乳动物细胞产生并分泌。在我们涉及β-APP重组表达的研究中，β-淀粉样蛋白产量的增加与异常β-APP分子的表达有关。β-淀粉样蛋白结构域内的缺失突变、成纤维细胞或神经元细胞中β-APP异构体的错误表达，或β-APP的过量表达均导致β-淀粉样蛋白产量增加。异常的β-APP似乎从分泌途径转向，然后降解为β-淀粉样蛋白。
