1. Brain Extracellular Matrix in Health and Disease
Action: BM1001
Years:
Brain Extracellular Matrix in Health and Disease
Participating countries: 18
Chair of the Action: Prof. Alexander Dityatev
Rapporteur: Prof. Srecko Gajovic
Science Officer: Dr. Magdalena Radwanska
Action Website:
Scientific background
In the central nervous system (CNS), extracellular matrix (ECM) molecules, including chondroitin sulfate proteoglycans, hyaluronic acid, link proteins, reelin, agrin, laminins and tenascins, along with their remodelling enzymes, such as metalloproteinases, are secreted by neural and non-neural cells into the extracellular space. By forming heterogeneous scaffolds, ECM molecules regulate diverse vital neural functions. During development, the ECM plays crucial roles in neural cell proliferation, migration and differentiation. In the mature brain, the ECM is critically involved in multiple forms of plasticity, including long-term potentiation and depression, homeostatic plasticity and metaplasticity. Furthermore, mutations/dysregulation in expression or activity of ECM molecules and/or extracellular proteases lead to pathological remodelling of ECM and contribute to glioma expansion and pathological plasticity in the brain of patients with epilepsy, stroke, schizophrenia, and mental retardation.
Objectives defined in the MoU
The objective of this Action is to understand the rapidly emerging role of the neural extracellular matrix in brain function and dysfunction, by synergising European research in this multidisciplinary domain. Specifically, it aims
to promote fundamental studies of cell type- and subcellular domain-specific ECM assembly and remodelling, and functional characterization of neural ECM molecules;
to facilitate interactions between basic research and clinical groups that would result in identification of novel mutations in ECM molecules linked to neurological or psychiatric disorders and exploration of the pathophysiological pathways activated by dysregulation in neuronal ECM;
to promote development and functional characterization of ECM-targeting drugs; ECM-mimicking peptides and three-dimensional scaffolds;
To train young researchers in the field of neural ECM.
Working Groups
WG1 “ECM Functions” is focusing on functional characterization of ECM molecules.
WG2 “ECM Tools” is working on the design and generation of new tools for ECM research.
WG3 “ECM Diseases” is studying the importance of ECM molecules for brain disorders.
WG4 “ECM Drugs” is working to identify available and promote development of new drug-like compounds, which can target ECM molecules and pathways involved in brain disorders.
WG5 “ECM Scaffolds” is focusing on development of new 3D ECM scaffold for in vitro studies and for implantation in the CNS. .
Scientific deliverables obtained due to networking
Dityatev A, Rusakov DA (2011) Molecular signals of plasticity at the tetrapartite synapse. Current Opinion in Neurobiology 21:
Capacity building due to networking
A database of COST experts in brain ECM, and associated know-how, instruments, genetically modified animals, proteins and other resources has been generated.