AMYLOID PRECURSOR IN ALZHEIMER DISEASE

主要的组织学损伤一直存在于脑部 阿尔茨海默病患者有神经原纤维缠结(NFT)和老年 斑块(SF)。尽管NFT也存在于其他 神经退行性疾病，最近使用 分子生物学方法表明，理解NFT 而SP可能为深入了解该病的病因提供了重要的见解。 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是主要的 SP的成分位于21号染色体的同一区域 这在家族性AD中改变，在散发性AD中重复。这个 淀粉样蛋白的积木，淀粉样蛋白的分解产物 前体蛋白，可能是泛素导向的结果 蛋白质分解系统。最近的研究表明， 泛素结合物存在于NFT中。其性质和功能 淀粉样蛋白前体在正常细胞生理学中的作用 下定决心。因为淀粉样前体的氨基酸序列 一旦问世，就可以生产出针对合成肽的抗体。 这些抗体将被用来识别哪些细胞产生 淀粉样蛋白前体以及它是否被泛素化。尽管NFT 和SP具有相同的表位，发现的淀粉样前体序列为 PHF可能与SP中的不同。淀粉样前体 是一种膜受体蛋白。从生理上讲，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 来自淀粉样前体的胞内结构域。因此， 很重要的一点是要知道抗病毒抗体是否 胞内结构域染色NFT和细胞骨架元件结合 这些序列。发现一种共同的形成机制 NFT和SP的合作将大大促进对 阿尔茨海默病的发病机制。

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.