PRODUCTION, PURIFICATION AND STRUCTURAL VALIDATION OF THE BDNF NEUROTROPHIN AND ITS RECOMBINANT PROISOFORMS WITH EMPHASIS IN DEPRESSIVE DISORDER

• Grant number: 24/14919-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Renê de Oliveira Beleboni
• Grantee: Aryanne Dias da Silva
• Host Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil
• Associated research grant: 23/05079-6 - Production, structural and functional validation of the BDNF neurotrophin and its recombinant proisoforms with emphasis in depressive disorder, AP.R

Abstract

Depression is a neuropsychiatric disorder that affects 10-20% of the world's population,and is therefore a serious universal public health problem. Although the understanding, diagnosisdiagnosis/monitoring and treatment of this disorder have progressed in recentdecades, much still needs to evolve for more significant advances to have an impact on the reality of medical practice and patients' health.medical practice and the health of patients. With regard to neurobiological explanations of depression,the modern complementation of the monoamine theory by the neurotrophin theory has pointed to theneurotrophic factor BDNF and its proisoforms as entities with great practical potential forbiomarker and/or treatment of the disorder. The BDNF factor is found in reduced levelsespecially in the hippocampus and prefrontal cortex of depressed patients, and rises in level after effectiveeffective treatment with conventional antidepressants. Blood levels of BDNFaccompany the reduction in brain content and the severity of the disorder, and also rise during the course of effective treatment.course of effective treatment. The aim of this work will be to arrange for the production andpurification of BDNF and its human and main pro-isoforms, as well as to provide structuralstructural validation of these assets with an innovative emphasis on the potential treatment/biomarkation of depression. Aheterologous production will take place in E. coli using pET-26b(+) expression plasmid vectors withexpected initial productivity in the mg/L range. Purification will be carried out usingaffinity chromatography on a nickel column. The active ingredients will then be quantified and analyzed for their degree of homogeneity.analyzed for degree of homogeneity/purity. Structural identification/validation willmass spectrometry. This project has significant biotechnologicalbiotechnological value, as well as great medical and industrial-pharmaceutical interest. Itmarket and establishes a production and biochemical-pharmacological study arrangementbiochemical-pharmacological study for innovative assets with a great future.