AAT Deficiency & Liver Diseases Caused by Proteins

AAT 缺乏症

• 批准号: 7114520
• 负责人: Bruce C Trapnell
• 金额: $ 3万
• 依托单位: ALPHA-1 FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-21 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114520
• 关键词: alpha 1 antitrypsin deficiency; inborn metabolism disorder; liver disorder; meeting /conference /symposium; molecular pathology; protein folding; travel

DESCRIPTION (provided by applicant): The Alpha-1 Foundation (A1F) and the American Association for the Study of Liver Diseases (AASLD) are organizing a Basic Research Single Topic Conference entitled "Alpha-1 Antitrypsin Deficiency and Other Liver Diseases Caused by Aggregated Proteins" on January 26-28, 2006. This conference focuses on an important, emerging topic: the molecular pathogenesis and therapy for Alpha-1 Antitrypsin (AAT) Deficiency and other inherited metabolic disorder of protein folding. The conference will include presentations by internationally recognized experts on the molecular pathogenesis of AAT Deficiency and other liver diseases associated with aggregated proteins. A primary goal is to stimulate a deeper understanding of the molecular mechanisms underlying these liver diseases to review and explore potential therapeutic approaches. This Basic Research Single Topic Conference is the culmination of an ongoing collaboration between the A1F and AASLD designed to to increase awareness of AAT Deficiency as well as increase the overall understanding of the underlying pathogenesis for a number of different liver diseases. This conference builds upon several previous symposia and conferences that the A1F and AASLD have held since 2000, including Alpha-1 Antitrypsin Deficiency and Other Conformational Diseases (June, 2000) and symposia during the 2003 and 2004 AASLD Annual Meetings on the Hepatotoxicity associated with Alpha-1 and Other Liver Diseases, and Insights into Metabolic Diseases. The 2006 conference will examine the recent contributions from basic research over the past 5 years that have improved our understanding of the mechanisms by which glycoproteins such as alpha-1 antitrypsin are correctly folded within the endoplasmic reticulum. The conference is also predicated by clinical data that is beginning to emerge that may explain the molecular basis for why some individuals with AAT Deficiency get liver disease and some do not. Another focus of the conference is the significant work in translational liver research that combines gene transfer technology and cell biology to create and evaluate hepatocyte transplantation therapeutic strategies for end stage liver diseases. The identified goals of the conference are to: 1) Understand the molecular biology of protein folding, the role of the protein degradation system, and the consequences of misfolding of specific proteins seen in several clinical disorders; 2) Discuss the current concepts of the molecular mechanisms responsible for liver injury in patients with Alpha-1 Antitrypsin Deficiency; 3) Explain the current molecular approaches underway to develop effective therapies to treat the liver manifestations of Alpha-1 Antitrypsin Deficiency and other disorders involving protein misfolding.

描述（由申请人提供）： Alpha-1基金会（A1F）和美国肝病研究协会（AASLD）正在组织一次基础研究单主题会议，题为“ Alpha-1抗胰蛋白酶缺乏症和其他综合蛋白质蛋白质的其他肝病”。蛋白质折叠的其他遗传代谢障碍。该会议将包括国际认可的专家关于AAT缺乏症的分子发病机理和与聚集蛋白有关的其他肝病的演讲。一个主要目标是刺激对这些肝脏疾病基础的分子机制的更深入了解，以审查和探索潜在的治疗方法。这次基础研究单一主题会议是A1F与AASLD之间正在进行的合作的结晶，旨在提高对AAT缺乏症的认识，并提高对许多不同肝脏疾病的基本发病机理的总体理解。这次会议是基于以前的几次研讨会和AASLD自2000年以来举行的会议和会议，包括Alpha-1抗胰蛋白酶缺乏症和其他构象疾病（2000年6月）和2004年AASLD年度会议期间与Alpha-1和其他Liversise和其他Liverises和其他Liverises和其他疾病相关的肝毒性，并在2003年和2004年的AASLD年度会议上进行了介绍。 2006年的会议将研究过去5年中基础研究的最新贡献，这些贡献提高了我们对糖蛋白（如α-1抗胰蛋白酶）在内质网中正确折叠的机制的理解。该会议还取决于临床数据开始出现的临床数据，这可能解释了某些AAT缺乏症患者会导致肝病而有些人没有的分子基础。会议的另一个重点是转化性肝脏研究中的重要工作，该研究结合了基因转移技术和细胞生物学，以创建和评估用于终末期肝脏疾病的肝细胞移植治疗策略。会议的确定目标是：1）了解蛋白质折叠的分子生物学，蛋白质降解系统的作用以及在几种临床疾病中看到的特定蛋白质错误折叠的后果； 2）讨论导致α-1抗胰蛋白酶缺乏症患者肝损伤的分子机制的当前概念； 3）解释目前正在开发有效疗法的分子方法，以治疗α-1抗胰蛋白酶缺乏症和其他涉及蛋白质错误折叠的疾病的肝脏表现。