ALTERNATIVE PROCESSING AND CHARACTERISTICS OF AMYLOID PRECURSOR PROTEIN

β-淀粉样蛋白(Abeta)，纤维的主要成分 老年人脑血管内老年斑和淀粉样沉积的组成 阿尔茨海默病(AD)和其他β-淀粉样蛋白相关疾病，是一种 较大前体APP的降解产物。阿贝塔在体内的沉积 脑血管壁和脑实质可能涉及复杂的相互作用 不同的细胞类型和不同的蛋白质因子。对…的理解 从Abeta前体和Abeta加工的机制 早期斑块和成熟斑块形成程度的测定 促进神经细胞损伤和疾病进展仍然是中心 以及对AD认识中的重要问题。最新发现来自 包括我们在内的不同群体，表明存在不同的应用程序 降解产物，其中一种只含有部分Abeta 序列(Nexin II)而另一个序列具有完整的Abeta， 因此，潜在的“淀粉样变性”。有趣的是，其中一些 包括Abeta和Nexin II在内的片段可以介导细胞黏附。我们发现 四肽RHDS可以模拟RGDS的行为，RGDS是一种广泛的 在许多细胞外发现的分布式细胞黏附识别信号 基质蛋白。 我们建议：1)鉴定中间APP C-末端片段(S) 通过免疫化学分析和N-末端序列含有Abeta；ii)至 使用这些信息来设计构造并将其表达在 为了获得足够数量的片段(S)用于细胞黏附 和酶降解/原纤维形成实验；iii)确定 RHDS序列对Nexin II和Abeta的生物学意义。

Beta-amyloid protein (Abeta), the major constituent of the fibrils composing senile plaques and amyloid deposits in cerebral blood vessels in Alzheimer's disease (AD) and other beta-amyloid related disorders, is a degradation product of a larger precursor APP. The deposition of Abeta in cerebral vessel wall and brain parenchyma may involve a complex interaction of different cell types and various protein factors. The comprehension of the mechanisms by which Abeta is processed from its precursor and the determination of the extent to which early and mature plaque formation contribute to neuronal cell damage and disease progression remain central and important questions in the understanding of AD. Recent findings from different groups including ours, indicate the existence of different APP degradation products, one of them containing only part of the Abeta sequence (nexin II) while another possess the intact Abeta being, therefore, potentially "amyloidogenic". Interestingly, some of these fragments including Abeta and nexin II can mediate cell adhesion. We found that the tetrapeptide RHDS can mimic the behavior of RGDS, a widely distributed cell adhesion recognition signal found in many extracellular matrix proteins. We propose i) to identify the intermediate APP C-terminal fragment(s) containing Abeta by immunochemical analysis and N-terminal sequence; ii) to use this information to engineering a construct and express it in cells in order to obtain enough amounts of fragment(s) to be used in cell adhesion and enzymatic degradation/fibril formation experiments; iii) to determine the biological importance of the sequence RHDS for both nexin II and Abeta.