ALTERNATIVE PROCESSING AND CHARACTERISTICS OF AMYLOID PRECURSOR PROTEIN

β-淀粉样蛋白（Abeta），原纤维的主要成分 在脑血管中形成老年斑和淀粉样沉积物， 阿尔茨海默病（AD）和其他β-淀粉样蛋白相关疾病是一种 一个较大的前体APP的降解产物。 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。 的理解 Abeta从其前体加工的机制， 确定早期和成熟斑块形成的程度 导致神经元细胞损伤和疾病进展仍然是中心 以及认识AD的重要问题。 最近的调查结果来自 包括我们在内的不同群体，表明存在不同的APP 降解产物，其中一种仅含有部分Abeta 序列（连接蛋白II），而另一个具有完整的A β， 因此可能是“淀粉样蛋白原性的”。 有趣的是， 包括Abeta和连接蛋白II的片段可以介导细胞粘附。 我们发现 四肽RHDS可以模拟RGDS的行为，这是一个广泛的研究领域。 分布的细胞粘附识别信号在许多细胞外 基质蛋白 我们建议i）鉴定中间APP C-末端片段 通过免疫化学分析和N-末端序列测定含有Abeta的蛋白质; ii） 用这些信息来设计一个结构，并在细胞中表达， 为了获得足够量的用于细胞粘附的片段 和酶降解/原纤维形成实验; iii）确定 RHDS序列对于连接蛋白II和Abeta的生物学重要性。

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.