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

• Grant number: 16/04912-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2016
• End date: July 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Giuliana da Silva Zuccoli
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/08711-3 - Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics, AP.JP
• Associated scholarship(s): 17/12558-7 - Employing CRISPR/Cas9 and Saccharomyces cerevisiae to understand energetic aspects of schizophrenia and antipsychotic treatment from a proteomic perspective, BE.EP.MS

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NASCIMENTO, JULIANA M.; GARCIA, SHEILA; SAIA-CEREDA, VERONICA M.; SANTANA, ALINE G.; BRANDAO-TELES, CAROLINE; ZUCCOLI, GIULIANA S.; JUNQUEIRA, DANIELLE G.; REIS-DE-OLIVEIRA, GUILHERME; BALDASSO, PAULO A.; CASSOLI, JULIANA S.; et al. Proteomics and molecular tools for unveiling missing links in the biochemical understanding of schizophrenia. PROTEOMICS CLINICAL APPLICATIONS, v. 10, n. 12, SI, p. 1148-1158, DEC 2016. (14/14881-1, 15/23049-0, 16/04912-2, 13/08711-3, 14/21035-0)

ZUCCOLI, GIULIANA S.; SAIA-CEREDA, VERONICA M.; NASCIMENTO, JULIANA M.; MARTINS-DE-SOUZA, DANIEL. The Energy Metabolism Dysfunction in Psychiatric Disorders Postmortem Brains: Focus on Proteomic Evidence. FRONTIERS IN NEUROSCIENCE, v. 11, SEP 7 2017. (16/04912-2, 13/08711-3, 14/10068-4, 14/21035-0, 16/07332-7)

NASCIMENTO, JULIANA M.; GARCIA, SHEILA; SAIA-CEREDA, VERONICA M.; SANTANA, ALINE G.; BRANDAO-TELES, CAROLINE; ZUCCOLI, GIULIANA S.; JUNQUEIRA, DANIELLE G.; REIS-DE-OLIVEIRA, GUILHERME; BALDASSO, PAULO A.; CASSOLI, JULIANA S.; et al. Proteomics and molecular tools for unveiling missing links in the biochemical understanding of schizophrenia. PROTEOMICS CLINICAL APPLICATIONS, v. 10, n. 12, p. 11-pg., 2016-12-01. (15/23049-0, 14/21035-0, 16/04912-2, 13/08711-3, 14/14881-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ZUCCOLI, Giuliana da Silva. Characterization of the mitochondrial and nuclear proteome of neural cells derived from iPSCs from schizophrenia patients. 2018. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.