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Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia

Abstract

Schizophrenia is a complex disease, likely to be caused by a combination of serial alterations in a number of genes and environmental factors. The dorsolateral prefrontal cortex (Brodmann's Area 46) is involved in schizophrenia and executes high-level functions such as working memory, differentiation of conflicting thoughts, determination of right and wrong concepts and attitudes, correct social behavior and personality expression. Global proteomic analysis of post-mortem dorsolateral prefrontal cortex samples from schizophrenia patients and non-schizophrenic individuals was performed using stable isotope labeling and shotgun proteomics. The analysis resulted in the identification of 1,261 proteins, 84 of which showed statistically significant differential expression, reinforcing previous data supporting the involvement of the immune system, calcium homeostasis, cytoskeleton assembly, and energy metabolism in schizophrenia. In addition a number of new potential markers were found that may contribute to the understanding of the pathogenesis of this complex disease.

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Acknowledgments

The authors would like to thank ABADHS (Associação Beneficente Alzira Denise Hertzog da Silva), FAPESP (Fundação de Amparo a Pesquisa do Estado de São Paulo), and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) for the financial support of this project in Brazil. We also would like to acknowledge the DAAD (Deutscher Akademischer Austauschdienst) and the Max Planck Society for their financial support of this work in Germany. We thank Ms. Molly McEwen for editorial help.

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Correspondence to Emmanuel Dias-Neto or Christoph W. Turck.

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Martins-de-Souza, D., Gattaz, W.F., Schmitt, A. et al. Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia. Eur Arch Psychiatry Clin Neurosci 259, 151–163 (2009). https://doi.org/10.1007/s00406-008-0847-2

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Keywords

  • schizophrenia
  • proteomics
  • shotgun
  • prefrontal cortex
  • biomarkers