FOR 1332: Physiological Functions of the APP Gene Family in the Central Nervous System

FOR 1332：APP 基因家族在中枢神经系统中的生理功能

• 批准号: 138733498
• 金额: --
• 依托单位: Institut für Pharmazie und Molekulare Biotechnologie (IPMB)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/138733498?language=en
• 关键词: 1332; Physiological; Functions; APP; Gene

The APP protein plays a key role in the pathogenesis of Alzheimers disease. Little is known, however, about its role for nerve cell communication in the healthy human brain. The purpose of the Research Unit is two-fold: to find out more about the proteins physiological role for learning and memory, and to enhance the understanding of APP functions with a view to developing new therapeutic approaches to treat Alzheimers disease. Alzheimers disease is triggered by deposits of insoluble protein aggregates that form plaques in the vicinity of nerve cells within the brains of Alzheimer patients. These plaques are mainly composed of the ß-amyloid peptide. The damage it inflicts on the nerve cells finally kills them. This small protein is derived via proteolysis from a much larger precursor, the amyloid precursor protein APP. So far, the normal cell biological and physiological functions of APP and its proteolytic products are largely unknown, although APP is produced in almost all brain cells, notably in regions important for memory formation. Recently, the enzymes involved in APP processing (termed secretases) have become major therapeutic AD targets and therapeutic interference with APP processing is likely to alter physiological APP functions. Thus, there is an urgent need for a dedicated research effort aimed at understanding the functional consequences of altered levels and activity of full length APP and its various proteolytic fragments in CNS physiology. Seven teams of scientists cooperate within the transregional Research Unit. They come from the universities of Heidelberg, Frankfurt/Main, Mainz and the technical universities of Kaiserslautern and Braunschweig. Using interdisciplinary methodological approaches the physiological functions of APP family proteins will be studied within the central nervous system from the molecular level to the intact organism. Within our highly interactive research projects we will study the role of APP family proteins in synapse formation and function, plasticity, learning and memory, neuroprotection and regeneration.

APP蛋白在阿尔茨海默病的发病机制中起着关键作用。然而，人们对它在健康人脑中神经细胞通讯中的作用知之甚少。研究单位的目的有两方面：一是进一步了解蛋白质在学习和记忆中的生理作用，二是加强对APP功能的了解，以期开发治疗阿尔茨海默病的新方法。阿尔茨海默病是由阿尔茨海默病患者大脑内神经细胞附近的不溶性蛋白质聚集体沉积形成斑块引发的。这些斑块主要由ß-淀粉样肽组成。它对神经细胞造成的伤害最终会杀死它们。这种小蛋白是由一个更大的前体淀粉样前体蛋白APP通过蛋白水解而产生的。迄今为止，APP及其蛋白水解产物的正常细胞生物学和生理功能在很大程度上是未知的，尽管APP几乎在所有脑细胞中产生，尤其是在记忆形成的重要区域。最近，参与APP加工的酶（称为分泌酶）已成为治疗AD的主要靶点，对APP加工的治疗干扰可能会改变APP的生理功能。因此，迫切需要专门的研究工作，旨在了解全长APP及其各种蛋白水解片段在中枢神经系统生理学中的水平和活性改变的功能后果。七个科学家小组在跨区域研究股内进行合作。他们分别来自海德堡大学、法兰克福大学、美因茨大学以及凯泽斯劳滕和布伦瑞克的技术大学。应用跨学科的方法，APP家族蛋白的生理功能将在中枢神经系统中从分子水平到完整的生物体进行研究。在我们高度互动的研究项目中，我们将研究APP家族蛋白在突触形成和功能、可塑性、学习和记忆、神经保护和再生中的作用。