ROLE OF SNAP25 IN THE CONTROL OF CALCIUM DYNAMICS: IMPLICATIONS FOR SCHIZOPHRENIA

Schizophrenia is a chronic, severe, and disabling brain disease. Ranking among the top 10 causes of disability in developed countries, schizophrenia affects one percent of the adult population, typically beginning in young adulthood, with hallucinations, delusions, social withdrawal, flattened emotions and loss of social and personal care skills. Evidence suggests that schizophrenia is a neurodevelopmental disease, involving interaction of several genes. In the last years the idea has established that the mechanisms responsible for schizophrenia may involve an alteration in the regulation of calcium ions, which represent the most relevant signalling pathway working in neurons. As a matter of fact, an altered calcium signalling may influence the formation, degeneration, and modification of neuronal processes, which convey and transfer information in brain. Furthermore, as neurons are especially sensitive to unregulated increases in the levels of intracellular calcium, an imbalance in this signaling may lead to cell death and could be at the basis of the reduction in the number of neurons observed in a percentage of patients affected by schizophrenia. Different molecules are modified in the brain of schizophrenic patients. One of these is the protein SNAP25, which is a component of the so-called SNARE complex, responsible for the release of neurotransmitters, i.e. the chemical messages which mediate communication between neurons in brain. Since many years, our laboratory is interested in defining the mechanisms which are involved in synaptic function. We have recently demonstrated that SNAP25 plays a relevant role in controlling levels of intracellular calcium in neurons. With this project, we aim at defining the mechanisms by which SNAP25 controls the calcium signalling pathway in neurons. If we will be able in doing that, then we will have a good hook to understand the molecular basis of schizophrenia, in the view of developing new approaches to treat the disease.