STRUCTURAL STUDY OF HUMAN AMYLOID PRECURSOR PROTEIN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 阿尔茨海默病S病是老龄化社会的一大健康问题。目前，它影响着这个国家的200万人。该病的分子机制尚不清楚，目前还没有有效的治疗方法。 遗传学研究表明，淀粉样前体蛋白(APP)的突变可能导致早发性和家族性疾病，从而涉及APP的发病机制。目前的一种假设是，这种突变会影响APP被分泌酶切割的方式，导致更多的淀粉样肽，这是APP的一种蛋白质分解片段，已知会在患病的脑组织中形成老年斑，长期以来一直被怀疑会导致神经退化。 拟议的实验旨在确定APP的原子结构，特别是受疾病突变影响的区域的原子结构。我们的目标是利用这些信息来帮助解释突变如何影响分泌酶对APP的切割能力，并确定可以稳定未切割的APP的因素，例如配体结合，从而防止APP转化为神经毒性淀粉样肽。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alzheimer¿¿¿s disease is a major health problem for the aging society. It currently affects 2 million people in this country. The molecular mechanism of the disease is not clear and there is no effective treatment as of today. Genetic studies indicated that mutations in amyloid precursor protein (APP) could cause early-onset and familial forms of the disease, thereby implicating APP in the disease mechanism. A current hypothesis is that such mutations affect how APP becomes cleaved by the secretases, resulting in more amyloid peptide, a proteolytic fragment of APP, which was known to form senile plaques in the diseased brain tissue and long suspected to cause neurodegeneration. The proposed experiment is designed to determine the atomic structure of APP, especially of the region that is affected by disease mutations. The goal is to use this information to help explain how mutations affect the cleavability of APP by the secretases and to identify factors, such as ligand binding, that could stabilize the uncut APP, thus preventing the conversion of APP to the neurotoxic amyloid peptide.