Molecular Identification of AMY, an Alzheimer Disease Amyloid‐Associated Protein
Molecular Identification of AMY, an Alzheimer Disease Amyloid‐Associated Protein
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阿尔茨海默病淀粉样蛋白相关蛋白 AMY 的分子鉴定
DOI：
10.1093/jnen/62.11.1108
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
J. Näslund
中科院分区：
文献类型：
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作者：
Linda Söderberg;V. Zhukareva;N. Bogdanovic;T. Hashimoto;B. Winblad;T. Iwatsubo;V. Lee;J. Trojanowski;J. Näslund
阿尔茨海默病 (AD) 的神经病理学病变特征之一是淀粉样 β-肽 (Aβ) 的脑积聚。尽管大量研究表明 Aβ 在体外自发形成淀粉样蛋白，但体内 Aβ 淀粉样蛋白形成的分子事件尚不清楚。免疫组织化学研究表明，其他蛋白质与 Aβ 共定位于大脑中的淀粉样蛋白沉积物中。其中一种蛋白质 AMY 的身份迄今为止仍然难以捉摸。因此我们尝试纯化AMY。人们发现 AMY 蛋白与人类 AD 大脑的不溶性组分中的 Aβ 共纯化，而在对照受试者的大脑中不存在。 AMY 免疫反应性主要限于 50 kDa 和 100 kDa 蛋白质种类。有趣的是，AMY 的色谱和免疫学特征与最近发现的淀粉样蛋白相关蛋白 CLAC 相似，CLAC 源自跨膜胶原样前体 CLAC-P。针对 AMY 的抗体可识别哺乳动物细胞中表达的 CLAC-P。此外，分别使用抗 AMY 和 CLAC 的抗体对 AD 脑切片和提取物进行并排比较，得到几乎相同的染色模式。因此，我们得出结论，AD 脑中与淀粉样蛋白相关的 AMY 免疫反应性是由于 CLAC 蛋白的存在。
One of the neuropathological lesions characteristic of Alzheimer disease (AD) is the cerebral accumulation of the amyloid β-peptide (Aβ). Although numerous studies have demonstrated that Aβ spontaneously forms amyloid in vitro, the molecular events underlying Aβ amyloid formation in vivo are less well understood. Immunohistochemical studies have shown that other proteins colocalize with Aβ in amyloid deposits in brain. The identity of one of these proteins, AMY, has so far remained elusive; therefore we attempted to purify AMY. The AMY protein was found to co-purify with Aβ in insoluble fractions from human AD brain, and was absent in brains from control subjects. AMY immunoreactivity was primarily restricted to a 50-kDa and 100-kDa protein species. Interestingly, the chromatographic and immunological profile of AMY resembled the recently identified amyloid-associated protein CLAC, derived from a transmembrane collagen-like precursor, CLAC-P. Antibodies against AMY recognized CLAC-P expressed in mammalian cells. In addition, side-by-side comparisons of AD brain sections and extracts, using antibodies against both AMY and CLAC, respectively, resulted in almost identical staining patterns. Therefore, we conclude that the AMY immunoreactivity seen in association with amyloid in AD brain is due to the presence of the CLAC protein.