Frameshift mutants of β amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients
Frameshift mutants of β amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients
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DOI：
10.1126/science.279.5348.242
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发表时间：
1998-01-09
期刊：
影响因子：
56.9
通讯作者：
Hol, EM
中科院分区：
文献类型：
--
作者：
van Leeuwen, FW;de Kleijn, DPV;Hol, EM
阿尔茨海默氏症和唐氏综合征患者的大脑皮层的特征是在神经原纤维缠结、神经斑块和神经丝中存在蛋白质沉积。这些结构被证明含有β淀粉样蛋白前体蛋白和泛素- b的形式，它们在羧基端是异常的（+1蛋白）。+1蛋白在年轻对照患者中未发现，而在老年对照患者中泛素- b +1的存在可能表明神经退行性变的早期阶段。这两种+1蛋白表现出细胞共定位，表明它们有共同的起源，在转录水平上起作用，或通过RNA的转录后编辑作用。这种类型的转录突变可能是广泛发生的非家族性早发性和晚发性阿尔茨海默病的重要因素。
The cerebral cortex of Alzheimer's and Down syndrome patients is characterized by the presence of protein deposits in neurofibrillary tangles, neuritic plaques, and neuropil threads. These structures were shown to contain forms of beta amyloid precursor protein and ubiquitin-B that are aberrant(+1 proteins) in the carboxyl terminus. The +1 proteins were not found in young control patients, whereas the presence of ubiquitin-B+1 in elderly control patients may indicate early stages of neurodegeneration. The two species of +1 proteins displayed cellular colocalization, suggesting a common origin, operating at the transcriptional level or by posttranscriptional editing of RNA. This type of transcript mutation is likely an important factor in the widely occurring nonfamilial early- and late-onset forms of Alzheimer's disease.