Studies of copper chelators for use in Alzheimer's therapy

• Grant number: 23/16251-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2024
• End date: June 30, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Giselle Cerchiaro
• Grantee: Giovana Brait Bertazzo
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Almost a century has passed since Alzheimer's disease (AD) was categorized as a form of dementia. Since then, its incidence has grown significantly, making it currently the most prevalent form of dementia, accounting for 60% to 70% of global cases. One of the main avenues of study into the causes of Alzheimer's disease is the formation of extracellular amyloid plaques, made up of ²-amyloid (A²) peptides. As these plaques accumulate, they block neural synapses, resulting in neurodegeneration. Studies indicate that transition metal ions, such as copper, can promote the aggregation of the A²42 peptide. In addition, although copper is essential for the body, when it is deregulated it can produce reactive oxygen species that cause cell damage. The considerable oxidative brain damage generated by the redox activity of copper and its influence on the aggregation of beta-amyloid plaques justifies the search for copper chelating agents as potential treatments in the early stages of AD. The aim of this work is to synthesize and characterize the copper ligands, carry out in vitro tests of the 3 new Cu(II) ligands and evaluate the cell toxicity of each ligand using the MTT method. In addition, ICP-MS (inductively coupled plasma mass spectrometry) analyses will be carried out to verify the removal of copper by the chelating agents in the cell culture and studies will be carried out into the damage to biomolecules (oxidative damage to proteins and lipids in cells and to DNA) prevented by the new ligands.