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

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。该研究单位的目的有两个：了解更多关于蛋白质在学习和记忆中的生理作用，并提高对APP功能的理解，以开发治疗阿尔茨海默病的新方法。阿尔茨海默病是由不溶性蛋白质聚集物沉积引发的，这些蛋白质聚集物在阿尔茨海默病患者大脑内的神经细胞附近形成斑块。这些斑块主要由β-淀粉样肽组成。它对神经细胞造成的伤害最终会杀死它们。这种小蛋白质是通过蛋白水解从一个更大的前体，淀粉样前体蛋白APP衍生。到目前为止，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，虽然APP是在几乎所有的脑细胞，特别是在区域重要的记忆形成。最近，参与APP加工的酶（称为分泌酶）已成为主要的治疗AD的目标和治疗干扰APP加工可能会改变生理APP功能。因此，迫切需要一个专门的研究工作，旨在了解的功能性后果的改变水平和活动的全长APP及其各种蛋白水解片段在中枢神经系统的生理。七个科学家小组在跨区域研究股内开展合作。他们来自海德堡大学、法兰克福/美因大学、美因茨大学以及凯泽斯滕和布伦瑞克的技术大学。利用跨学科的方法，APP家族蛋白质的生理功能将在中枢神经系统内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。

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.