Characterization of the mitochondrial proteome and oxidative biochemical profile of neural cells derived from iPSCs from patients with schizophrenia

Abstract

Schizophrenia is a severe and incurable mental disorder that affects 1% of the world's population, characterized by genes that promote vulnerability and environmental injuries, such as infections, toxins, traumas, and stress during pregnancy or childhood. Proteomic studies, investigate proteins and their levels of expression, on cells, tissues and organisms, have provided perspectives and new hypothesis on the molecular basis of the disease's physiopathology. Evidences suggest that energy metabolism dysfunctions, combined with oxidative stress and mitochondrial dysfunction during neurodevelopment, could explain some of the features observed on the disease, such as deficient connectivity and neural synchronization. This study aims to untangle the mitochondrial biochemical profile, by state-of-the-art proteomic techniques, using neural progenitor cells (NPCs) and neurons, derived from induced pluripotent stem cells (iPSC) from schizophrenia patients, comparing to healthy subjects. Thus, we aim to elucidate altered events during neurodevelopment and on the mature neuron, which could be related to schizophrenia disturbances. The production of reactive oxygen species (ROS) and the quantitative profile of cellular antioxidant defenses will also be evaluated. The present study will contribute to the understanding of molecular mechanisms involved in the pathophysiology of schizophrenia, through the integration of biochemical pathways and identification of key-molecules for the disease. Furthermore, those molecules could be studied separately, potentially bringing new insigths into therapeutic and diagnostic targets. (AU)