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Obtaining and characterizing peptides with neuroprotective activity

Grant number: 17/16977-4
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): June 01, 2018
Effective date (End): March 14, 2021
Field of knowledge:Agronomical Sciences - Food Science and Technology - Food Science
Principal Investigator:Maria Teresa Bertoldo Pacheco
Grantee:Maria Elisa Caetano Silva Abreu
Host 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
Associated scholarship(s):19/17269-9 - Study of whey peptides activity in the inhibition of microglia activation in cell culture model, BE.EP.PD


The Alzheimer's Disease (AD) is a progressive and irreversible neuropathology that has been affected more and more people, especially over 65 years old. The progression of the disease results from the aggregation of amyloid-² peptide, their assembly into amyloid fibrils and the consequent formation of senile plaques. In parallel, activation of the resident immune cells of the central nervous system (microglia) can occur, with the release of inflammatory cytokines. Thus, in the last years, several studies have been targeted on new antifibrillar and anti-inflammatory agents for therapeutic applications. Based on current knowledge, some metallic ions, such as copper, iron, and zinc, are considered to trigger the ²-amyloid peptide aggregation. Therefore, our hypothesis is that 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. This study aims to obtain and characterize new whey peptides with neuroprotective activity, acting in some factors closely related to the establishment and development of the AD. For this purpose, it will be evaluated the peptides from bovine whey protein. Whey protein isolate (WPI) will be hydrolyzed with Alcalase® and ultrafiltered to obtain peptides with low molecular mass (MM < 5 kDa). The peptides with metal-binding ability (Cu, Fe, and Zn) will be isolated by immobilized metal affinity chromatography (IMAC), in an FPLC system, and sequenced by mass spectrometry (MALDI-TOF/TOF). The peptides will be evaluated by in vitro assays of aggregation of amyloid-ß peptides inhibition, in the presence or absence of metal ions, and microglia activation assays using cell culture model. The peptides will be also evaluated by their antioxidant (ORAC and DNA protection) and anticholinesterase activities, related to the decrease in oxidative stress and the decrease of the acetylcholine degradation, respectively. The peptides whose show positive results can be synthesized and evaluated for their neuroprotection potential using the same techniques described. 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.

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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)
ROJAS, MELIZA LINDSAY; KUBO, MIRIAN T. K.; CAETANO-SILVA, MARIA ELISA; AUGUSTO, PEDRO E. D.. Ultrasound processing of fruits and vegetables, structural modification and impact on nutrient and bioactive compounds: a review. INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY, v. 56, n. 9, SI, p. 4376-4395, . (17/16977-4, 19/05043-6)
CAETANO-SILVA, MARIA ELISA; SIMABUCO, FERNANDO MOREIRA; NEVES BEZERRA, ROSANGELA MARIA; DA SILVA, DANIELE CRISTINA; BARBOSA, EDER ALVES; MOREIRA, DANIEL CARNEIRO; BRAND, GUILHERME DOTTO; DE SOUZA DE ALMEIDA LEITE, JOSE ROBERTO; BERTOLDO PACHECO, MARIA TERESA. Isolation and Sequencing of Cu-, Fe-, and Zn-Binding Whey Peptides for Potential Neuroprotective Applications as Multitargeted Compounds. Journal of Agricultural and Food Chemistry, v. 68, n. 44, p. 12433-12443, . (18/14818-9, 17/16977-4, 16/06457-0)

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