Scholarship 21/08883-5 - Cobre, Doença de Alzheimer - BV FAPESP
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New copper chelators for use in Alzheimer's Disease therapy: in vitro and cellular studies

Grant number: 21/08883-5
Support Opportunities:Scholarships in Brazil - Doctorate
Start date until: July 01, 2022
End date until: May 31, 2025
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Giselle Cerchiaro
Grantee:Mariana Leticia Munin Camargo
Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Copper is an essential trace element for the proper functioning of the human body, but it must have strictly well-regulated homeostasis, otherwise it can play a fundamental role in neurodegenerative diseases that occur due to its deficiency or accumulation in the brain. Alzheimer's Disease is the most common case of dementia, a neurodegenerative disease that presents with symptoms such as memory loss and language difficulties, and can occur from genetic causes or sporadically. The main characteristic of brains affected by Alzheimer's is the accumulation of the ²-amyloid protein fragment, called ²-amyloid plaques, outside the neurons. Research indicates that a failure in copper homeostasis can lead to metal overload in the brain, which is directly linked to the formation of these plaques. Knowing the role that copper plays in Alzheimer's Disease, several researches have focused on the study of chelators for the treatment of the disease, but many are restricted to molecules that already exist. Thus, the objective of this research is to prepare new selective copper chelators and investigate their efficiency in removing the metal ion from beta-amyloid fibrils, so that they can be candidates for drugs in the treatment of Alzheimer's Disease. For this, competition studies will be carried out with beta-amyloid protein by EPR and UV-Vis, cellular studies of complexation and neurodegeneration inhibition, through techniques such as ICP-MS Western Blotting and flow cytometry, and, finally, studies in animals. (AU)

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