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Study of whey peptides activity in the inhibition of microglia activation in cell culture model

Grant number: 19/17269-9
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): January 31, 2020
Effective date (End): October 30, 2020
Field of knowledge:Agronomical Sciences - Food Science and Technology
Principal Investigator:Maria Teresa Bertoldo Pacheco
Grantee:Maria Elisa Caetano Silva Abreu
Supervisor abroad: Rodney Wayne Johnson
Home Institution: Instituto de Tecnologia de Alimentos (ITAL). Agência Paulista de Tecnologia dos Agronegócios (APTA). Secretaria de Agricultura e Abastecimento (São Paulo - Estado). Campinas , SP, Brazil
Local de pesquisa : University of Illinois at Urbana-Champaign, United States  
Associated to the scholarship:17/16977-4 - Obtaining and characterizing peptides with neuroprotective activity, BP.PD

Abstract

The progression of the Alzheimer Disease (AD) results from the aggregation of the amyloid-beta peptide (AB42), their assembly into amyloid fibrils and the consequent formation of senile plaques. This process can culminate in the activation of the resident immune cells of the central nervous system (microglia), with the consequent release of inflammatory cytokines. Thus, in the last years, several studies have been targeted on new antifibrillar and anti-inflammatory agents for therapeutic applications. Metallic ions, such as copper, iron, and zinc, are considered to trigger the ²-amyloid peptide aggregation, therefore, mineral chelating agents, as bioactive peptides of food origin, may promote the reduction of fibrils formation, as well as act in the inhibition of neuroinflammation. The present proposal of Research Internship Abroad aims to evaluate the neuroprotective activity of whey peptides and their possible mechanisms in the inhibition of microglia activation. Peptides with metal-binding ability (Cu, Fe, and Zn) were previously isolated by immobilized metal affinity chromatography (IMAC) and purified by RP-HPLC and the chromatographic fractions are in the phase of sequencing and synthesis of the most promisor sequence. In the present project, microglia cells of primary culture will be treated with peptides (chromatographic extracts or synthetic peptide) and their activation will be stimulated by the application of LPS or AB42. Then it will be evaluated the alteration of cellular morphology, by confocal microscopy, as well as the following markers: nitric oxide production (using DAF-FM-DA probe), expression of TNF-A and IL-1B (qRT-PCR, immunocytochemistry and ELISA) and release of extracellular glutamate. This project proposes to identify bioactivities not yet studied to whey peptides, providing a subsidy for future studies in the treatment of neurodegenerative diseases with food-derived peptides.