Study of Molecular and Cellular Mechanisms in Mental Disorders: Clinical Studies and Animal Models.

• Grant number: 25/01121-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2025
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Mirian Akemi Furuie Hayashi
• Grantee: Ingrid Sancho de Farias
• 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 potentially severe and highly prevalent conditions that affect the central nervous system (CNS). Studies investigating biochemical, molecular, and/or cellular alterations could aid in improving diagnostic accuracy and in better understanding the neurobiology involved in MDs. This, in turn, could lead to the identification of potential new targets for the development of innovative drugs that may enable more effective treatment of symptoms or even their cure and/or the possible prevention of this pathological condition, which currently has no known cure and limited treatment options.Over the past years, analyses using patient samples or animal models for the study of schizophrenia (SCZ) have demonstrated that oligopeptidases, such as Ndel1, play a fundamental role in brain formation and in the progression of MDs like SCZ. The importance of this oligopeptidase's activity in neuritogenesis and neuronal migration during embryogenesis and brain formation, as well as the significant differences in the activity of various oligopeptidases (Ndel1, ACE, and POP) in animal models and in patients with SCZ, bipolar disorder, and/or first-episode psychosis compared to their respective healthy controls, has been demonstrated mainly by our group in recent years as part of this thematic project's activities.At this stage of the project, the identification of specific inhibitors for Ndel1 through high-throughput screening (HTS) and/or via a cyclic peptide library (produced in my doctoral research) would be crucial for significant progress in this thematic project. This approach would enable the study of the role of these oligopeptidases in vivo, potentially contributing to the identification of natural substrates of these enzymes. The identified inhibitors would allow for the inhibition of endogenous Ndel1 in human neuroblastoma cells (SK-N-AS lineage) and in animal models of MDs, thereby enabling the determination or further elucidation of this oligopeptidase's function in neuronal and/or brain physiology and pathology. Additionally, it would allow for comparisons with clinical findings in patients with SCZ and/or related MDs (such as depression, bipolar disorder, and crack cocaine users).