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Enzymatic activity of oligopeptidases Ndel1 and/or ACE in plasma or blood serum of patients with depression and bipolar disorder

Grant number: 23/06934-7
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2023
Effective date (End): January 31, 2024
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


The etiology of depression and bipolar disorder is complex, and their development is dependent of both genetic and ambiental factors. Their pathophysiology is still not fully understood, as well as there is 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 hypothesis recognized to explain the development of these diseases. 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. Therefore, the motivation to study the oligopeptidases Ndel1 (Nuclear distribution element-like 1) and angiotensin converting enzyme 1 (ACE) activity in patients with depression and bipolar disorder 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 on Ndel1 and ACE oligopeptidase activity in individuals in first episode of psychosis or with schizophrenia were already been demonstrated. So forth, we believe that the evaluation of the activity of these enzymes in individuals with depression and bipolar disorder 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.

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