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Studies of copper in neurodegenerative diseases

Grant number: 19/04799-0
Support Opportunities:Scholarships abroad - Research
Start date: July 01, 2019
End date: July 31, 2019
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Giselle Cerchiaro
Grantee:Giselle Cerchiaro
Host Investigator: Rosanna Squitti
Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
Institution abroad: Ospedale San Giovanni Calibita Fatebenefratelli, Italy  

Abstract

Strong evidence in the scientific literature suggests that the deterioration of essential transition metal homeostasis, increasing oxidative damage to biomolecules by redox imbalance, is closely related to the onset, maintenance, and evolution of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Although these connections are recognized, the major metabolic mechanisms behind these pathologies remain unknown. Our goal is to determine the mechanism behind the flow and accumulation of metal in the cell during the early stages of neurodegenerative disease, especially Alzheimer's disease. To reach this goal, a multidimensional analysis is necessary, relating chemical, analytical and metabolomic data.To reach this objective, and thinking within a longer and larger project, international collaboration with one of the leading experts in the field is necessary, as previously indicated by FAPESP (application number 2018/03781-7). In this project, we intend to study a molecular and chemical response in cellular neurodegeneration, through blood samples from patients with Alzheimer's and their relationship with copper transporter proteins, especially with mutations in ATP7A (recently discovered by the group of Dr. Squitti) . Following this study, conducted in the Fatebenefratelli hospital in Rome, Italy, in partnership with the leading researcher in the field, Dr. Rosanna Squitti, it is intended in Brazil to continue collaboration through the insertion of the mutated ATP7-A gene into neuronal cells of the hippocampus in order to perform molecular studies of the interaction of this cell with reactive oxygen species, with destabilization of intracellular metal homeostasis and with alterations in metabolism. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
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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)
SILVA, DANIELA ALMEIDA DA; DE LUCA, ANASTASIA; SQUITTI, ROSANNA; RONGIOLETTI, MAURO; ROSSI, LUISA; MACHADO, CAMILA M. L.; CERCHIARO, GISELLE. Copper in tumors and the use of copper-based compounds in cancer treatment. Journal of Inorganic Biochemistry, v. 226, . (19/04799-0, 20/14175-0)