Downregulation of GNA13-ERK network in prefrontal cortex of schizophrenia brain identified by combined focused and targeted quantitative proteomics
作者： Mio Hirayama-Kurogi , Yohei Takizawa , Yasuto Kunii , Junya Matsumoto , Akira Wada
DOI: 10.1016/J.JPROT.2017.02.009
关键词:
摘要: Abstract Schizophrenia is a disabling mental illness associated with dysfunction of the prefrontal cortex, which affects cognition and emotion. The purpose present study was to identify altered molecular networks in cortex schizophrenia patients by comparing protein expression levels autopsied brains controls, using combination targeted focused quantitative proteomics. We selected 125 molecules possibly related for quantification knowledge-based Among quantified molecules, GRIK4 MAO-B were significantly decreased plasma membrane cytosolic fractions, respectively, cortex. Focused proteomics identified 15 increased 39 proteins. Network analysis “GNA13-ERK1-eIF4G2 signaling” as downregulated network, proteins involved this network decreased. Furthermore, searching downstream eIF4G2 revealed that eIF4A1/2 CYFIP1 decreased, suggesting downregulation suppresses CYFIP1, regulates actin remodeling axon outgrowth spine formation. Downregulation signaling seems likely impair formation synapse plasticity neuronal cells, could be development cognitive impairment pathology schizophrenia. Biological significance compared proteome between healthy controls means global Targeted MAOB among putatively schizophrenia-related patients. Global 54 differentially expressed brains. profile indicates attenuation “GNA13-ERK brain. In particular, EIF4G2 are located GNA13-ERK signal may cause brain Our results provide novel insight into pathology, helpful drug development.
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