Succinilação e malonilação de proteínas na esquizofrenia

Author(s)

Bradley Joseph Smith

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2019-01-28

Examining board members

Daniel Martins de Souza; Alessandro dos Santos Farias; Lucilene Delazari dos Santos

• Advisor: Daniel Martins de Souza

Abstract

Schizophrenia is a multifactorial mental disorder that affects nearly 1% of the population worldwide. Patients are negatively affected in various ways; and there is no known cure for this disease. Pathways associated with energy metabolism are dysregulated, and metabolic disruption is also one of the side effects of antipsychotics, the principal way to manage the symptoms of schizophrenia. In 2011 two post-translational protein modifications, the succinylation and malonylation of lysine residues, were discovered to be widely present in likely all domains of life and furthermore have been observed on many proteins associated with glycolysis and metabolism. The precursors to these modifications, understood to be succinyl-CoA and malonyl-CoA, are also both a part of central metabolic processes, and their prevalence as a modification in cells can vary with metabolism-associated stimuli, such as hypoxia, a potential environmental trigger for developing schizophrenia. In this work, shotgun mass spectrometry-based quantitative proteomics was used to determine what differences in succinyllysine and malonyllysine profiles exist under various conditions. Postmortem brain tissue of schizophrenia patients was compared with tissue from mentally sound controls. Additionally, human oligodendrocyte precursor cell cultures (MO3.13 lineage) were treated with MK-801 and/or 3 antipsychotics and analyzed. The differences uncovered herein can potentially provide insight into the etiology, pathophysiology, symptoms, and treatment of schizophrenia (AU)

• FAPESP's process: 16/07948-8 - Relationship between a myelin-associated phosphodiesterase CNP and schizophrenia
• Grantee: Bradley Joseph Smith
• Support Opportunities: Scholarships in Brazil - Master