Oligodendrocytes: Potential of Discovering New Treatment Targets

Autor(es)

Brandao-Teles, Caroline ^[1] ; de Almeida, Valeria ^[1] ; Cassoli, Juliana S. ^{[1, 2]} ; Martins-de-Souza, Daniel ^{[3, 1, 4]}

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Lab Neuroprote, Campinas, SP - Brazil

^[2] Fac Palmas, Palmas - Brazil

^[3] UNICAMPs Neurobiol Ctr, Campinas, SP - Brazil

^[4] Conselho Nacl Desenvolvimento Cient & Tecnol, Inst Nacl Biomarcadores Neuropsiquiatria, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN PHARMACOLOGY; v. 10, MAR 5 2019.
• Citações Web of Science: 1

Resumo

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 (R) 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. (AU)

• Processo FAPESP: 17/25588-1 - Da compreensão básica a biomarcadores clínicos para a esquizofrenia: um estudo multidisciplinar centrado na neuroproteômica
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/14881-1 - Compreensão da influência de componentes da via glicolítica na função dos oligodendrócitos: uma relação com os achados em esquizofrenia
• Beneficiário: Juliana Silva Cassoli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/23049-0 - Unindo culturas de oligodendrócitos humanos e disfunção do sistema glutamatérgico para compreender as bases moleculares da esquizofrenia
• Beneficiário: Caroline Brandão Teles Rodrigues
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/18242-1 - Vias bioquímicas moduladas por drogas canabinóides em oligodendrócitos humanos
• Beneficiário: Valéria de Almeida
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/10068-4 - EMU concedido no processo 13/08711-3: espectrômetro de massas Waters SYNAPT G2-Si HDMs + nanoACQUITY UPLC
• Beneficiário: Daniel Martins-de-Souza
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários