Transcriptional Regulators in the Cerebellum in Chronic Schizophrenia: Novel Possible Targets for Pharmacological Interventions

Despite the emerging role of transcriptional regulators in schizophrenia as key mo lecular effectors re-sponsible for the dysregulation of multiples biological processes, limited information is available in brain are-as that control higher cognitive functions as the cerebellum. To identify transcription factors that could control a wide panel of altered proteins in the cerebellar cortex in schizophrenia, we analyzed a dataset obtained us-ing one-shot liquid chromatography-tandem mass spectrometry on postmortem human cerebellar cortex in chronic schizophrenia (PXD024937 identifier in ProteomeXchange repository). Our analysis revealed a panel of 11 enriched transcription factors (SP1, KLF7, SP4, EGR1, HNF4A, CTCF, GABPA, NRF1, NFYA, YY1) and MEF2A, that could be controlling 250 altered proteins. The top 3 significantly enriched transcription factors were SP1, YY1, and EGR1 and the transcription factors with the largest number of targets were SP1, KLF7 and SP4 which belong to the Krüppel superfamily. An enrichment in vesicle-mediated transport was found for SP1, KLF7, EGR1, HNF4A, CTCF and MEF2A targets while pathways related to signaling, inflamma-tion/immune response, apoptosis, and energy were found for SP1 and KLF7 targets. EGR1 targets were en-riched in RNA processing and, GABPA and YY1 targets were mainly involved in organelle organization and assembly. This study provides a reduced panel of transcriptional regulators that could be impacting on multi-ple pathways through the control of a number of targets in the cerebellum in chronic schizophrenia. These findings suggest that this panel of transcription factors could be key targets for pharmacological interventions in schizophrenia.