Studies of copper in neurodegenerative diseases

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