Altered CSNK1E, FABP4 and NEFH protein levels in the dorsolateral prefrontal cortex in schizophrenia

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• 作者：Raquel Pinacho^a ; Nú ; ria Villalmanzo^a ; J. Javier Meana^b ; Isidre Ferrer^c ; Adriana Berengueras^d ; Josep M. Haro^a ; Judit Villé ; n^e ; Belé ; n Ramos^a ; ^{bramos@fsjd.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Schizophrenia ; Postmortem dorsolateral prefrontal cortex ; Proteomics ; CSNK1E ; FABP4 ; NEFH
• 刊名：Schizophrenia Research
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：177
• 期：1-3
• 页码：88-97
• 全文大小：669 K

文摘

Schizophrenia constitutes a complex disease. Negative and cognitive symptoms are enduring and debilitating components of the disorder, highly associated to disability and burden. Disrupted neurotransmission circuits in dorsolateral prefrontal cortex (DLPFC) have been related to these symptoms. To identify candidates altered in schizophrenia, we performed a pilot proteomic analysis on postmortem human DLPFC tissue from patients with schizophrenia (n = 4) and control (n = 4) subjects in a pool design using differential isotope peptide labelling followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). We quantified 1315 proteins with two or more unique peptides, 116 of which showed altered changes. Of these altered proteins, we selected four with potential roles on cell signaling, neuronal development and synapse functioning for further validation: casein kinase I isoform epsilon (CSNK1E), fatty acid-binding protein 4 (FABP4), neurofilament triplet H protein (NEFH), and retinal dehydrogenase 1 (ALDH1A1). Immunoblot validation confirmed our proteomic findings of these proteins being decreased in abundance in the schizophrenia samples. Additionally, we conducted immunoblot validation of these candidates on an independent sample cohort comprising 23 patients with chronic schizophrenia and 23 matched controls. In this second cohort, CSNK1E, FABP4 and NEFH were reduced in the schizophrenia group while ALDH1A1 did not significantly change. This study provides evidence indicating these proteins are decreased in schizophrenia: CSNK1E, involved in circadian molecular clock signaling, FABP4 with possible implication in synapse functioning, and NEFH, important for cytoarchitecture organization. Hence, these findings suggest the possible implication of these proteins in the cognitive and/or negative symptoms in schizophrenia.