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Altered serine/threonine kinase activity in schizophrenia
Jennifer L McGuire1, John H Hammond2, Stefani D Yates2
1Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA.
Brain Research
|May 1, 2014
Summary
Schizophrenia involves altered signaling pathways. A new kinase array platform revealed widespread changes in protein kinase activity in the brain, offering new drug targets for this psychiatric disorder.
Area of Science:
- Neuroscience
- Biochemistry
- Psychiatry
Background:
- Schizophrenia etiology involves multiple signaling pathway alterations.
- Previous studies were limited to analyzing few phosphoproteins.
- Simultaneous analysis of signaling cascades is needed.
Purpose of the Study:
- To simultaneously investigate multiple signaling cascades in schizophrenia.
- To identify differentially phosphorylated peptide substrates in the frontal cortex.
- To explore potential drug targets for schizophrenia treatment.
Main Methods:
- Utilized a novel kinase array platform to assess >100 serine/threonine protein kinase activities.
- Analyzed frontal cortex tissue from schizophrenia patients.
- Employed Ingenuity Pathway Analysis (IPA) for functional grouping of phosphopeptides.
Main Results:
- Identified 19 differentially phosphorylated peptide substrates (>15% change) in the frontal cortex.
- Pathway analysis revealed involvement in cellular homeostasis (14 peptides), cytoskeletal organization (10 peptides), and ion homeostasis (8 peptides).
- This is the first study to comprehensively investigate signaling cascade changes in schizophrenia.
Conclusions:
- Comprehensive analysis of kinase activity provides novel insights into schizophrenia pathophysiology.
- Findings highlight the role of cellular homeostasis, cytoskeletal, and ion homeostasis pathways.
- This approach may facilitate the discovery of new drug targets for schizophrenia treatment.
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