Biochemical Pathways Triggered by Antipsychotics in Human [corrected] Oligodendrocytes: Potential of Discovering New Treatment Targets.

Autor: Brandão-Teles C; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil., de Almeida V; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil., Cassoli JS; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; Faculdade de Palmas, Palmas, Brazil., Martins-de-Souza D; Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil.; UNICAMP's Neurobiology Center, Campinas, Brazil.; Instituto Nacional de Biomarcadores em Neuropsiquiatria, Conselho Nacional de Desenvolvimento Científico e Tecnológico, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Frontiers in pharmacology [Front Pharmacol] 2019 Mar 05; Vol. 10, pp. 186. Date of Electronic Publication: 2019 Mar 05 (Print Publication: 2019).
DOI: 10.3389/fphar.2019.00186
Abstrakt: Schizophrenia is a psychiatric disorder that affects more than 21 million people worldwide. It is an incurable disorder and the primary means of managing symptoms is through administration of pharmacological treatments, which consist heavily of antipsychotics. First-generation antipsychotics have the properties of D 2 receptor antagonists. Second-generation antipsychotics are antagonists of both D 2 and 5HT 2 receptors. Recently, there has been increasing interest in the effects of antipsychotics beyond their neuronal targets and oligodendrocytes are one of the main candidates. Thus, our aim was to evaluate the molecular effects of typical and atypical drugs across the proteome of the human oligodendrocyte cell line, MO3.13. For this, we performed a mass spectrometry-based, bottom-up shotgun proteomic analysis to identify differences triggered by typical (chlorpromazine and haloperidol) and atypical (quetiapine and risperidone) antipsychotics. Proteins which showed changes in their expression levels were analyzed in silico using Ingenuity ® Pathway Analysis, which implicated dysregulation of canonical pathways for each treatment. Our results shed light on the biochemical pathways involved in the mechanisms of action of these drugs, which may guide the identification of novel biomarkers and the development of new and improved treatments.
Databáze: MEDLINE