Abstract
Mental disorders (MDs) are a group of potentially serious and highly prevalent diseases affecting the Central Nervous System (CNS). Studies that seek biochemical/molecular and/or cellular alterations could help in the diagnosis accuracy, as well as for the better understanding of the neurobiology involved in the MDs, thus allowing the possible identification of potential new targets for the development of innovative drugs that enable higher efficacy of the symptoms treatment, or even the MDs cure and/or possible prevention. Over the last few years, analyzes of cells maintained in culture and/or patient samples or animal models for schizophrenia (SCZ) have demonstrated that oligopeptidases, such as Ndel1, play a key role in brain formation and progression of MDs, as SCZ. The importance of oligopeptidase activity for neuritogenesis and for neuronal migration during embryogenesis and brain formation, as well as the significant differences in these oligopeptidases activity in SCZ patients compared to healthy controls, also observed in animal models for SCZ, have been demonstrated mainly by our group in last few years. At this stage of the project, we propose to carry out molecular and cellular studies, including bioinformatics analyzes, that may help to identify the pathways specifically altered in SCZ. We also propose a general evaluation of animal models (transgenics or knockouts), before and after treatment with psychostimulants and/or antipsychotics (including innovative treatments), in order to compare them with the clinical alterations already described by the group so far. We hope that this work will enable a cutting-edge new understanding of altered pathways in MD patients, with a special focus in SCZ. (AU)
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