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Protein Succinylation and Malonylation as Potential Biomarkers in Schizophrenia

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Author(s):
Joseph Smith, Bradley ; Brandao-Teles, Caroline ; Zuccoli, Giuliana S. ; Reis-de-Oliveira, Guilherme ; Fioramonte, Mariana ; Saia-Cereda, Veronica M. ; Martins-de-Souza, Daniel
Total Authors: 7
Document type: Journal article
Source: JOURNAL OF PERSONALIZED MEDICINE; v. 12, n. 9, p. 15-pg., 2022-09-01.
Abstract

Two protein post-translational modifications, lysine succinylation and malonylation, are implicated in protein regulation, glycolysis, and energy metabolism. The precursors of these modifications, succinyl-CoA and malonyl-CoA, are key players in central metabolic processes. Both modification profiles have been proven to be responsive to metabolic stimuli, such as hypoxia. As mitochondrial dysfunction and metabolic dysregulation are implicated in schizophrenia and other psychiatric illnesses, these modification profiles have the potential to reveal yet another layer of protein regulation and can furthermore represent targets for biomarkers that are indicative of disease as well as its progression and treatment. In this work, data from shotgun mass spectrometry-based quantitative proteomics were compiled and analyzed to probe the succinylome and malonylome of postmortem brain tissue from patients with schizophrenia against controls and the human oligodendrocyte precursor cell line MO3.13 with the dizocilpine chemical model for schizophrenia, three antipsychotics, and co-treatments. Several changes in the succinylome and malonylome were seen in these comparisons, revealing these modifications to be a largely under-studied yet important form of protein regulation with broad potential applications. (AU)

FAPESP's process: 14/10068-4 - Multi-User Equipment approved in grant 13/08711-3: mass spectrometer waters SYNAPT G2-Si HDMS + nanoACQUITY UPLC
Grantee:Daniel Martins-de-Souza
Support Opportunities: Multi-user Equipment Program
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
FAPESP's process: 17/25055-3 - The role of hnRNPs in oligodendrocytes and their implications on schizophrenia
Grantee:Caroline Brandão Teles Rodrigues
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 15/23049-0 - Employing human oligodendroglial cell cultures and glutamatergic dysfunction to understand the molecular basis of schizophrenia
Grantee:Caroline Brandão Teles Rodrigues
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 18/01410-1 - Evaluating the effects of clozapine on immune system cells
Grantee:Guilherme Reis-De-Oliveira
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 18/14666-4 - Influence of the endocannabinoid system on the energetic profile of neural cells during neurodevelopment: implications in Schizophrenia
Grantee:Giuliana da Silva Zuccoli
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 19/05747-3 - Maintaining and maturing oligodendrocyte cell line
Grantee:Bradley Joseph Smith
Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
FAPESP's process: 16/07332-7 - The role of 14-3-3 and Ephrin signaling pathways on cellular communication between neurons-astrocytes and the functioning of the synapse tripartite
Grantee:Verônica Aparecida Monteiro Saia Cereda
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 13/08711-3 - Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics
Grantee:Daniel Martins-de-Souza
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 19/00098-7 - Multi-User Equipment approved in grant 2017/25588-1: cromatógrafo Acquity UPLC I-Class
Grantee:Daniel Martins-de-Souza
Support Opportunities: Multi-user Equipment Program
FAPESP's process: 17/25588-1 - From the basic understanding to clinical biomarkers to schizophrenia: a neuroproteomics-centered multidisciplinary study
Grantee:Daniel Martins-de-Souza
Support Opportunities: Research Projects - Thematic Grants