Functions of the Alzheimer Key Protein APP

The APP protein plays a key role in the pathogenesis of Alzheimer’s disease. Little is known, howver, about its role for nerve cell communication in the healthy human brain. A new interdisciplinary and transregional research group is investigating the “Physiological Functions of the APP Gene Family in the Central Nervous System“. The purpose is two-fold: to find out more about the protein’s physiological role for learning and memory, and to enhance the understanding of APP functions with a view to developing new therapeutic approaches to treat Alzheimer´s disease. The German Research Foundation (DFG) will be providing the research unit with funding in the amount of 1.96 million euros over a period of three years. Project coordinator is Prof. Dr. Ulrike Müller of Heidelberg University.

Alzheimer’s disease is triggered by deposits of unsoluble 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.

The aim of the new integrated research project is to employ an interdisciplinary approach to achieve a better understanding of the physiological functions of APP from the molecular level to its role in the intact nervous system. “Our intention is to investigate the role of APP and its proteolytic products for the formation and functioning of synapses, notably with regard to learning and memory,” says Prof. Müller of the Institute of Pharmacy and Molecular Biotechnology. The scientists also want to find out what role APP and related proteins play in the prevention of damage to nerve cells and their regeneration. “There is still no therapy for the causes of Alzheimer’s. Accordingly, a better understanding of the physiological functions of APP is essential for the development of innovative treatment strategies,” says Prof. Müller.

Seven teams of scientists cooperate within the research unit on “Physiological Functions of the APP Gene Family in the Central Nervous System”. They come from the Universities of Heidelberg, Frankfurt/Main, Mainz and the Technical Universities of Kaiserslautern and Braunschweig. At Heidelberg University, two research groups from the biosciences are involved. The team headed by Prof. Müller is analysing the role of the APP gene family in the central nervous system using genetically modified mouse models. In a joint project with Prof. Dr. Thomas Deller of Frankfurt University, Prof. Müller is investigating the role of APP for neuronal regeneration processes after damage to the central nervous system, while the research group headed by Dr. Klemens Wild at the Heidelberg University Biochemistry Center is using X-ray structural analysis to study the spatial structure of APP. At Heidelberg’s Faculty of Medicine, Prof. Dr. Andreas Draguhn’s team is looking into the function performed by APP for synaptic communication in neuronal networks. This project is being conducted at the Institute of Physiology and Pathophysiology.

Contact
Prof. Dr. Ulrike Müller
Institute of Pharmacy and Molecular Biotechnology
phone: +49 6221 546717
u.mueller@urz.uni-hd.de

Communications and Marketing
Press Office, phone: +49 6221 542311
presse@rektorat.uni-heidelberg.de

For further information, go to http://www.ipmb.uni-heidelberg.de.