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Free keywords:
OLIGODENDROCYTE DYSFUNCTION; GENE; POSTMORTEM; EXPRESSION; CORTEX;
NETWORKS; MATTER; MAPPsychiatry; Oligodendrocytes; myelin; proteome; pathway; drug target;
Abstract:
Objectives Disturbances in the myelin sheath drive disruptions in neural transmission and brain connectivity as seen in schizophrenia. Here, the myelin proteome was characterised in schizophrenia patients and healthy controls to visualise differences in proteomic profiles. Methods A liquid chromatography tandem mass spectrometry-based shotgun proteomic analysis was performed of a myelin-enriched fraction of postmortem brain samples from schizophrenia patients (n = 12) and mentally healthy controls (n = 8).In silicopathway analyses were performed on the resulting data. Results The present characterisation of the human myelinome led to the identification of 480 non-redundant proteins, of which 102 proteins are newly annotated to be associated with the myelinome. Levels of 172 of these proteins were altered between schizophrenia patients and controls. These proteins were mainly associated with glial cell differentiation, metabolism/energy, synaptic vesicle function and neurodegeneration. The hub proteins with the highest degree of connectivity in the network included multiple kinases and synaptic vesicle transport proteins. Conclusions Together these findings suggest disruptive effects on synaptic activity and therefore neural transmission and connectivity, consistent with the dysconnectivity hypothesis of schizophrenia. Further studies on these proteins may lead to the identification of potential drug targets related to the synaptic dysconnectivity in schizophrenia and other psychiatric and neurodegenerative disorders.
