Study of Metabolic Syndrome on clozapine treated adipocytes

• Grant number: 18/03450-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2019
• End date: December 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Daniel Martins-de-Souza
• Grantee: Aline Gazzola Fragnani Valença
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/25588-1 - From the basic understanding to clinical biomarkers to schizophrenia: a neuroproteomics-centered multidisciplinary study, AP.TEM

Abstract

Schizophrenia is an incurable psychiatric illness that affects about 1% of the world's population. The symptoms usually appear in adult life and are divided into three categories: positive symptoms (hallucinations and delusions); negative symptoms (unsociability, depression and lack of motivation); and cognitive problems (difficulty concentrating, impaired executive functions and long-term memory failure). The treatment is usually performed with antipsychotics that are often inefficient or have many side effects. Clozapine is an antipsychotic known for its efficacy in relieving the symptoms of treatment-resistant patients. However, the drug can cause serious side effects and some patients may develop a metabolic syndrome, the most common symptoms of which include fast weight gain, cardiovascular problems and diabetes. Our project aims to treat human adipocytes with clozapine and to analyze 1) its proteomic profile in order to verify the biochemical pathways altered by the drug and 2) the expression profile of miRNAs, since the last have been described as endocrine signaling in tissue adipose. Our goal is to find molecular signatures that could elucidate the mechanisms of action by which clozapine causes metabolic syndrome in patients and, in the future, use that knowledge to associate the drug with the attenuating components and/or provide insights to improve the drug or even create a new drug. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FALVELLA, ANA CAROLINE BRAMBILLA; SMITH, BRADLEY JOSEPH; SILVA-COSTA, LICIA C.; VALENCA, ALINE G. F.; CRUNFLI, FERNANDA; ZUARDI, ANTONIO W.; HALLAK, JAIME E.; CRIPPA, JOSE A.; ALMEIDA, VALERIA DE; MARTINS-DE-SOUZA, DANIEL. Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. FRONTIERS IN MOLECULAR NEUROSCIENCE, v. 14, MAY 28 2021. (18/03422-7, 08/09009-2, 17/18242-1, 19/00098-7, 17/25588-1, 19/22398-2, 18/10362-0, 18/03450-0, 18/03673-0)