EXTRABRAIN · Extracellular brain proteolysis in neuronal plasticity and neuropsychiatric disorders

Brain disorders comprise a major burden for the society. Recent analyses of the neuropsychiatric disease-related gene polymorphisms as well as genomics and proteomics have identified the components of the extracellular matrix (ECM) and the cell adhesion molecules (CAMs) in the brain as pivotal for those diseases. The ECM/CAMs span the synaptic cleft and regulate the synaptic dynamics. Furthermore, recent studies have shown that proteolytic activity may release from the ECM/CAMs cryptic ligand(s) that activate cell surface receptors and initiate intracellular signalling cascade(s). Thus, ECM and its enzymatic modifications have emerged as a highly topical research area, also because their extracellular localization makes the development of enzymatic inhibitors more feasible. This proposal brings together a group of well-established academic and industrial partners sharing interest in the ECM and its proteolysis. In the proposal there is clearly an overlapping interest in specific brain conditions and structures to be investigated, making the consortium ideally suited to provide a comprehensive picture for the role of ECM proteolysis in brain function and dysfunctions. While the academic partners focus on specific research questions, the industrial members are to provide the entire consortium with high-throughput techniques and powerful research tools. This combination of conceptual scientific vision, tools and approaches should be of great benefit for the young researchers to be trained. The trainees will be exposed to courses, workshops, joint research meetings and inter-laboratory visits. The focus of the training program is on expanding knowledge and on developing new treatments to anxiety disorders, schizophrenia, mental retardation and Alzheimer’s. A unifying neurobiological concept in the consorted effort to tackle these conditions is the involvement of abnormal synaptic plasticity.