Related Experiment Video
Updated: Apr 30, 2026
Standardized Data Acquisition for Neuromelanin-Sensitive Magnetic Resonance Imaging of the Substantia Nigra
Published on: September 8, 2021
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.
Abstract:
Converging evidence implicates alterations in multiple signaling pathways in the etiology of schizophrenia. Previously, these studies were limited to the analysis of one or a few phosphoproteins at a time. Here, we use a novel kinase array platform to simultaneously investigate the convergence of multiple signaling cascades implicated in schizophrenia. This technology uses consensus peptide substrates to assess activity levels of a large number (>100) of serine/threonine protein kinases. 19 peptide substrates were differentially phosphorylated (>15% change) in the frontal cortex in schizophrenia. These peptide substrates were examined using Ingenuity Pathway Analysis to group them according to the functions and to identify processes most likely affected in schizophrenia. Pathway analysis placed 14 of the 19 peptides into cellular homeostatic pathways, 10 into pathways governing cytoskeletal organization, and 8 into pathways governing ion homeostasis. These data are the first to simultaneously investigate comprehensive changes in signaling cascades in a severe psychiatric disorder. The examination of kinase activity in signaling pathways may facilitate the identification of novel substrates for drug discovery and the development of safer and more effective pharmacological treatment for schizophrenia.
Insights
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.
Related Concept Videos
01:27Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within...
01:29Biological Causes of Schizophrenia
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin...
01:02Phosphorylation
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
01:30Positive Symptoms of Schizophrenia: Hallucinations and Delusions
Thought Disorders
Disorganized and unusual thought processes mark thought disorders in schizophrenia. One key feature is disorganized speech, where an individual's conversation includes...
01:28Psychosis and Antipsychotic Drugs: Overview
01:29Psychological and Sociocultural Causes of Schizophrenia