The study of oligopeptidases in schizophrenia

• Grant number: 13/18805-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: September 30, 2013
• End date: December 29, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Mirian Akemi Furuie Hayashi
• Grantee: Camila Miyagui Yonamine Asanuma
• Supervisor: Opher Gileadi
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: University of Oxford, England
• Associated to the scholarship: 12/08941-6 - The study of oligopeptidases in schizophrenia, BP.PD

Abstract

Schizophrenia (SCZ) is a severe chronic mental disease. The current body of evidence suggests that it is a multifactorial disease with genetic and environmental factors, leading to an altered neurodevelopment. Ndel1 (nuclear-distribution element-like 1) is an oligopeptidade that binds to Disrupted-in-Schizophrenia 1 (DISC1) gene product, which has been largely studied as a SCZ vulnerability marker. Interestingly, the expression of Ndel1 was found reduced in hippocampus of schizophrenic patients. POP (prolyloligopeptidase) was also found decreased in plasma of schizophrenic patients, and it has also been considered as a potential drug target for the treatment of several mental diseases, including depression and SCZ. The ACE (angiotensin I-converting enzyme) was also related to SCZ, because drug-free patients showed significantly lower levels of ACE in cerebrospinal fluid (CSF) than the neuroleptic-treated patients. The spontaneously hypertensive rats (SHRs) have been proposed as an animal model for the screening of drugs with therapeutic potential for treatment of disorders of cognitive processes. Thus, our primary objective is to compare the plasma Ndel1, POP, and ECA enzyme activity levels of patients with SCZ and healthy controls (HCs). These same measures will also be evaluated in SHR rats to elucidate the similarities between this animal model and human patients, aiming a better understanding of the molecular mechanisms underlying this mental dysfunction. (AU)