Establishment of the hnRNPs role on schizophrenia through protein interaction network mapping

Abstract

Schizophrenia consists on a chronic psychiatric disorder reaching 1% of world population. It is a multifactorial disease resulting of environmental and genetic factors. The pathology molecular mechanisms are mostly unknown, therefore several methodologies such as GWAS, transcriptome and proteome has been used to study and better understand the molecular basis concerning schizophrenia.Our group compared brains from patients with schizophrenia with brains from normal individuals and showed that brains with schizophrenia presents several up- and down-regulated proteins belonging to the hnRNP class. Moreover, our group showed differential hnRNPs in oligodendrocytes when treat with clozapin, a common psychotic used in schizophrenia treatment, pointing to a role of hnRNP in schizophrenia.Therefore, this project aims to use co-immunoprecipitation and chemical cross-linking methodologies to map the interaction network of hnRNPs. Interactome studies will be performed in oligodendrocytes as well as in post mortem tissues of corpus callosum from individuals with and without schizophrenia.A second step will contemplate a functional study of identified targets in the first part of the project. The CRISPR-Cas9 method will be used to mutate interacting partners in oligodendrocytes, causing alterations in these complexes that will be correlated to their respective functions. Therefore, this project aims, through the use of two innovative approaches, to improve the biochemical knowledge about this poorly understood disease. (AU)