STRUCTURAL STUDY OF HUMAN AMYLOID PRECURSOR PROTEIN

点击翻译按钮获取中文摘要

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.