STRUCTURAL STUDY OF HUMAN AMYLOID PRECURSOR PROTEIN

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 阿尔兹海默症老年痴呆症是老龄化社会的一个主要健康问题。它目前影响着这个国家的200万人。该病的分子机制尚不清楚，目前尚无有效的治疗方法。 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，从而暗示APP在疾病机制中。目前的假设是，这种突变影响APP如何被分泌酶切割，导致更多的淀粉样肽，APP的蛋白水解片段，已知其在患病的脑组织中形成老年斑，长期以来被怀疑导致神经变性。 该实验旨在确定APP的原子结构，特别是受疾病突变影响的区域。目的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APP的因素，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.