Enzymatic activity of oligopeptidases Ndel1 and/or ACE in plasma or blood serum of patients with Depression

• Grant number: 22/00527-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2022
• End date: March 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Mirian Akemi Furuie Hayashi
• Grantee: Larissa Ribino Parra
• 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

The etiology of Depression is complex, and its development is dependent on both genetic and ambient factors. Depression is considered one of the most debilitating mental diseases and actually, and more than 200 million individuals around the world are affected. However, its pathophysiology is still not fully understood, as well as there are no biomarkers to support the diagnosis. Also, the pharmacological treatment is limited, as it is still based on modulating the monoaminergic neurotransmission. The noradrenergic, serotoninergic, and/or monoaminergic pathways' disbalance is one of the few hypotheses recognized to explain the development of the disease. However, other pathways, including the neuropeptidergic, could be potentially involved in depression, as well as studies have already suggested and demonstrated the association of neuropeptide neurotransmission in schizophrenia and bipolar disorder. Therefore, the motivation to study the oligopeptides Ndel1 (Nuclear distribution element-like 1) and angiotensin-converting enzyme 1 (ACE) activity in patients with depression is based on the fact that these enzymes are neuropeptidases, cleaving neuropeptides as the neurotensin, which has already been demonstrated to be fundamental for the response to the antipsychotics, besides being also considered as an endogenous antipsychotic. The neuropeptidergic pathway can modulate the monoaminergic transmission, and alterations in Ndel1 and ACE oligopeptidase activity in individuals in the first episode of psychosis or with schizophrenia or bipolar disorder were already been demonstrated. So forth, we believe that the evaluation of the activity of these enzymes in individuals with depression can contribute to the knowledge and understanding of the etiology underlying depression. In addition, it might also allow us to observe the differences and/or similarities between different mental diseases, such as depression, schizophrenia, and bipolar disorder.(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)

HAYASHI, MIRIAN A. F.; SALVETAT, NICOLAS; CAYZAC, CHRISTOPHER; CHECA-ROBLES, FRANCISCO JESUS; DUBUC, BENJAMIN; MEREUZE, SANDIE; V. NANI, JOAO; MOLINA, FRANCK; BRIETZKE, ELISA; WEISSMANN, DINAH. Euthymic and depressed bipolar patients are characterized by different RNA editing patterns in blood. PSYCHIATRY RESEARCH, v. 328, p. 4-pg., 2023-08-27. (19/08287-3, 22/03297-3, 19/09207-3, 19/13112-8, 20/01107-7, 22/00527-8, 17/02413-1, 14/50891-1)

SANTIAGO, THAYS CALISTA; PARRA, LARISSA; NANI, JOAO V.; FIDALGO, THIAGO M.; BRADSHAW, NICHOLAS J.; HAYASHI, MIRIAN A. F.. Angiotensin-converting enzymes as druggable features of psychiatric and neurodegenerative disorders. Journal of Neurochemistry, v. 166, n. 2, p. 18-pg., 2023-03-27. (19/08287-3, 22/03297-3, 19/09207-3, 19/13112-8, 20/01107-7, 22/00527-8, 17/02413-1, 14/50891-1)