NON-A-BETA COMPONENT OF ALZHEIMERS-DISEASE AMYLOID (NAC) IS AMYLOIDOGENIC
NON-A-BETA COMPONENT OF ALZHEIMERS-DISEASE AMYLOID (NAC) IS AMYLOIDOGENIC
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DOI：
10.1021/bi00032a006
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发表时间：
1995-08-15
期刊：
影响因子：
2.9
通讯作者：
SAITOH, T
中科院分区：
文献类型：
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作者：
IWAI, A;YOSHIMOTO, M;SAITOH, T
阿尔茨海默病(AD)淀粉样蛋白(NAC)的非Aβ成分被生化鉴定为从AD患者脑组织中提纯的淀粉样蛋白的第二主要成分。NAC由其140个氨基酸的前体NACP衍生而来，至少有35个氨基酸长(NAC35)，尽管其氨基端尚未确定。针对NAC35的氨基末端9个氨基酸序列，制备了抗NAC-X1抗血清，并经肽亲和层析纯化。这种亲和纯化的抗NAC-X1抗体免疫染色AD脑切片上的淀粉样蛋白，在Western或斑点杂交上识别NAC35而不识别NACP。在水溶液中，合成的NAC35以时间、浓度和温度依赖的方式自聚集。最初检测到的NAC35是一种分子质量为3500 Da的单体，但随着时间的推移聚集成不能迁移到凝胶中的较高分子质量组分。经刚果红染色后的NAC35聚集体在偏振光下分析时呈现绿金色双折射，超微结构分析时呈现纤维状结构。这些结果表明，NAC可以在其前体被切割后形成淀粉样蛋白，这可能是AD大脑中淀粉样蛋白病的关键因素。
The non-A beta component of Alzheimer's disease (AD) amyloid (NAC) was identified biochemically as the second major component in the amyloid purified from brain tissue of AD patients. NAC, derived from its 140 amino acid long precursor, NACP, is at least 35 amino acids long (NAC35) although its amino terminus is not definitely determined. An antiserum, anti-NAC-X1, was raised against the amino-terminal 9 amino acid sequence of NAC35 and purified on a peptide affinity column. This affinity-purified anti-NAC-X1 antibody immunostained amyloid in AD brain sections and recognized NAC35 but not NACP on Western or dot blot. In aqueous solutions, synthetic NAC35 self-aggregated in a time-, concentration-, and temperature-dependent manner. NAC35 was detected initially as a monomer with a molecular mass of 3500 Da but became aggregated as a function of time into a higher molecular mass component that could not migrate into the gel. The aggregate of NAC35 showed green-gold birefringence after Congo red staining when analyzed under polarized light and fiber-like structure when analyzed ultrastructually. These results suggest that NAC can form amyloid after it has been cleaved out of its precursor and may be a crucial factor in amyloidosis in the AD brain.