Effector of APP to Lower Amount of beta-Amyloid Protein

APP 降低 β-淀粉样蛋白含量的效应器

• 批准号: 6648997
• 负责人: Frederick S Hagen
• 金额: $ 36.99万
• 依托单位: ICOGENEX CORPORATION
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-15 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6648997
• 关键词: Alzheimer's disease; amyloid proteins; biomaterial development /preparation; biotechnology; cell line; complementary DNA; flow cytometry; fluorescence microscopy; peptides; polymerase chain reaction; protein biosynthesis; protein structure function; tissue /cell culture; transfection /expression vector

DESCRIPTION (provided by applicant): Alzheimer's disease is a devastating common disorder affecting primarily elderly people with a prevalence of five percent of the population over sixty-five, increasing to twenty percent over the age of eighty. An estimated ten million people in the world have the disease, at a cost of $65 billion for U.S. patients in 1995. The prevalence and the cost continue to escalate with increase in the mean age of the population. Currently, there is no cure for Alzheimer's disease and treatments are palliative rather than treating the underlying causes of the disease. An over production of beta-amyloid (A beta), a natural occurring peptide processed from beta-amyloid precursor protein (APP), is the central key factor in the development of Alzheimer's. Factors influencing over production of A beta increase the prevalence and early onset of Alzheimer's. Most current drug development programs are focused on affecting the activities of the processing enzymes to cause a reduction in A beta. However, these processing enzymes are also involved in other important biological processes. A change in processing activity predicts other health problems, in a novel approach, proposed research would identify a structure that binds to APP altering its conformation and processing to cause reduction in the abundance of A beta. Such a specific approach and the evidence from identified genetic changes in APP that affect early onset of Alzheimer's with lack of any other apparent health problem, predict a high utility of such an anti-Alzheimer's therapeutic.

描述（由申请人提供）：阿尔茨海默病是一种毁灭性的常见疾病，主要影响老年人，患病率为65岁以上人口的5%，80岁以上增加到20%。据估计，全世界有1000万人患有这种疾病，1995年美国患者的费用为650亿美元。随着人口平均年龄的增加，患病率和费用继续上升。目前，阿尔茨海默氏病没有治愈方法，治疗是姑息性的，而不是治疗疾病的根本原因。β-淀粉样蛋白（A β）的过度产生是阿尔茨海默氏症发展的核心关键因素，A β是一种由β-淀粉样蛋白前体蛋白（APP）加工而成的天然肽。影响A β过度产生的因素增加了阿尔茨海默氏症的患病率和早发性。 目前大多数药物开发计划都集中在影响加工酶的活性，以减少A β。然而，这些加工酶也参与其他重要的生物过程。加工活动的变化预测其他健康问题，在一种新的方法中，拟议的研究将确定一种与APP结合的结构，改变其构象和加工，导致A β丰度减少。这种特定的方法和来自APP中鉴定的影响阿尔茨海默氏症早期发作而没有任何其他明显健康问题的遗传变化的证据预测了这种抗阿尔茨海默氏症治疗剂的高效用。