Novel strategies for the treatment of schizophrenia based on genetic variation of the neural cell adhesion molecule NCAM and enzymes involved in its posttranslational modifications
Functional dysconnectivity plays a key role in the pathogenesis and aetiology of schizophrenia. Compelling evidence links aberrations in the expression and modification of the neural cell adhesion molecule NCAM to schizophrenia. Studies in mice with mutations that influence NCAM expression and modification reveal the vital role of this complex molecular unit in establishing intact adaptive brain circuitries. Consequently, NCAM and the enzymes involved in its modification are promising targets for the development of causal therapeutic strategies. In the frame of NeuConnect a unique new schizophrenic patient database will be used to identify novel disease-associated variations in genes encoding NCAM and enzymes involved in its modification. The contribution of identified variants to discrete cognitive domains within the schizophrenic population will be analyzed. To gain molecular insight into NCAM regulated processes, patient data will be linked to studies on animal models designed to recapitulate the respective dysfunctions and thus leading to increased vulnerability. The proposed research project was set up to disclose novel pathogenic mechanisms. The highly interdisciplinary approach ranging from molecular studies to clinical aspects provides a perfect platform for translating accumulated knowledge of NCAM functions into effective therapeutic strategies for the treatment of schizophrenia. This is in full compliance with the aims of the call.
cellular and genetic approaches, Schizophrenia and psychotic disorders, Imaging techniques, Molecular, Animal models, Behavioural, Electrophysiology, Pharmacology
2011 - 2014
Rita Gerardy-Schahn (Coordinator)