Study of molecular and cellular mechanisms of mental disorders: clinical studies and animal models

• Grant number: 23/07904-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2023
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Mirian Akemi Furuie Hayashi
• Grantee: William Yoshio Agliardi Oyadomari
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 19/13112-8 - Study of molecular and cellular mechanisms involved in mental disorders: clinical and animal models analysis, AP.TEM

Abstract

Mental disorders (MDs) are a group of potentially serious and highly prevalent diseases that affect the Central Nervous System (CNS). Studies that seek biochemical/molecular and/or cellular alterations could help in the accuracy of the diagnosis, and also in a better understanding of the neurobiology involved in TMs, thus enabling the possible identification of potential new targets for the development of innovative drugs that could allow more effective treatment of symptoms, or even the cure and/or possible prevention of these illness with no cure yet. Over the past few years, analyzes employing culture cells and/or samples from patients or animal models for schizophrenia (SCZ), have shown that oligopeptidases, such as Ndel1, play a fundamental role in brain formation and progression of TMs, such as SCZ. The importance of oligopeptidase activity for neuritogenesis and for neuronal migration during embryogenesis and brain formation, and also the significant differences in the activity of oligopeptidases (such as Ndel1, ACE and POP) in SCZ patients compared to healthy controls, as well as in animal models for SCZ, were mainly demonstrated by our group in recent years.The identification of specific inhibitors for Ndel1 by high throughput screening (HTS) and/or employing a library of cyclic peptides (produced in my doctoral project) would be fundamental for the progress of this thematic project, by allowing the study of the role of this oligopeptidase in vivo, potentially contributing to the identification of natural substrates of this oligopeptidase. The identified inhibitors would also allow the inhibition of endogenous Ndel1 in human neuroblastoma (SK-N-AS) cells and in animal models for MDs, making it possible to determine the function of this oligopeptidase for morphology and pathology, aiming at comparison with clinical trials findings in SCZ and in correlated MDs (such as depression, bipolar disorder and crack users). (AU)

Scientific publications

(4)

(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)

OYADOMARI, WILLIAM Y.; CARVALHO, ELIZANGELA A.; MACHADO, GABRIEL E.; MACHADO, ANA JULIA O.; SANTOS, GABRIEL S.; MARCONDES, MARCELO; OLIVEIRA, VITOR. Towards a Survival-Based Cellular Assay for the Selection of Protease Inhibitors in Escherichia coli. BIOTECH, v. 14, n. 1, p. 10-pg., 2025-03-07. (23/07904-4, 20/09678-3, 21/11936-3, 23/09167-7)

OYADOMARI, WILLIAM Y.; CHRISTOFF, RAISSA R.; RABELLO, TAILENE; OLIVEIRA, VITOR; HIGA, LUIZA M.; GARCEZ, PATRICIA P.; HAYASHI, MIRIAN A. F.. Infection by zika virus increase angiotensin I-converting enzyme activity in mouse brain. Biochimie, v. 227, p. 3-pg., 2024-12-03. (20/01107-7, 19/13112-8, 23/07904-4, 17/02413-1, 19/08287-3, 14/50891-1, 22/03297-3, 19/09207-3, 22/00527-8)

NANI, JOAO V.; COELHO, CAMILA; OYADOMARI, WILLIAM Y.; SANTIAGO, THAYS CALISTA; MACHADO, MARCELO MARCONDES; CHRISTOFF, RAISSA R.; GARCEZ, PATRICIA P.; OLIVEIRA, VITOR; WURTELE, MARTIN; HAYASHI, MIRIAN A. F.. Identification of an ex vivo inhibitor of the schizophrenia biomarker Ndel1 by high throughput screening. Biochemical Pharmacology, v. 217, p. 11-pg., 2023-10-14. (19/09207-3, 23/07904-4, 20/01107-7, 22/00527-8, 17/02413-1, 19/08287-3, 22/03297-3, 19/13112-8, 14/50891-1)

OYADOMARI, WILLIAM Y.; SANTIAGO, THAYS C.; BASSO, LEONARDO; OLIVEIRA, VITOR; CRUZ, FABIO C.; NANI, JOAO, V; HAYASHI, MIRIAN A. F.. Long-term treatment with haloperidol modulates angiotensin I-converting enzyme (ACE) activity in transgenic animal model with construct validity for schizophrenia studies. Brain Research, v. 1859, p. 8-pg., 2025-04-17. (19/13112-8, 20/01107-7, 19/08287-3, 24/04617-7, 17/02413-1, 14/50891-1, 19/09207-3, 23/07904-4, 22/03297-3, 22/00527-8)