AMYLOID PRECURSOR IN ALZHEIMER DISEASE

主要的组织学病变始终发现在大脑中的 阿尔茨海默病患者是神经元缠结（NFT）和老年人， 斑块（SF）。 虽然NFT也存在于其他 神经退行性疾病，最近的结果获得使用 分子生物学方法表明， 和SP可能提供了一个重要的洞察的病因， 阿尔茨海默病（AD）。 这些研究表明， 编码淀粉样蛋白前体的基因，主要 SP组分，位于21号染色体的同一区域 在家族性AD中改变，在散发性AD中重复。 的 淀粉样蛋白的组成部分，淀粉样蛋白的分解产物 前体蛋白，可能是由泛素介导的 蛋白水解系统 最近的研究表明， 泛素缀合物存在于NFT中。 性质与作用 淀粉样蛋白前体在正常细胞生理学中的作用还没有被 测定 因为淀粉样蛋白前体的氨基酸序列 发表后，可以生产针对合成肽的抗体。 这些抗体将被用来识别哪些细胞产生 淀粉样蛋白前体和它是否是泛素化的。 虽然NFT 和SP共享表位，发现的淀粉样蛋白前体序列是 PHF可能与SP中发现的PHF不同。 是膜受体蛋白。 从生理学上讲，这种蛋白质 类与细胞骨架相互作用。 细胞骨架的存在 NFT中的元素可能是序列存在的直接结果， 从淀粉样蛋白前体的胞内结构域。 因此，我们认为， 重要的是要知道是否有抗 胞内结构域染色NFT和细胞骨架元件是否结合 这些序列。 发现一个共同的形成机制 NFT和SP的研究将大大促进对 AD的发病机制。

The major histological lesions consistently found in the brains of Alzheimer patients are neurofibrillary tangles (NFT) and senile plaques (SF). Although NFT are also found in other neurodegenerative conditions, recent results obtained using molecular biological approaches suggest that understanding the NFT and SP may provide an important insight into the etiology of Alzheimer disease (AD). These studies have demonstrated that the gene coding for the protein precursor of amyloid, the major component of SP, is located in the same region of chromosome 21 that is altered in familial AD and duplicate in sporadic AD. The building block of amyloid, a breakdown product of the amyloid precursor protein, possibly results from the ubiquitin-directed proteolytic system. Recent studies have demonstrated that ubiquitin conjugates are present in NFT. The nature and function of the amyloid precursor in normal cell physiology has not been determined. Since the amino acid sequence of the amyloid precursor is published, antibodies to synthetic peptides can be produced. These antibodies will be used to identify which cells produce amyloid precursor and whether it is ubiquitinated. Although NFT and SP share epitopes, the sequences of amyloid precursor found is PHF may not be identical to those found in SP. Amyloid precursor is a membrane receptor protein. Physiologically, proteins of this class interact with the cytoskeleton. The presence of cytoskeletal elements in NFT may be a direct result of the presence of sequences from the intracellular domain of the amyloid precursor. Therefore, it will be important to know whether antibodies to the intracellular domain stain NFT and if cytoskeletal elements bind to these sequences. The finding of a common mechanism of formation of both NFT and SP would advance substantially the understanding of the pathogenesis of AD.