Influence of the removal of essential transition metals and the presence of cell prion protein (PrPC) in protein aggregation in astrocytes

• Grant number: 18/22063-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2019
• End date: January 31, 2020
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Giselle Cerchiaro
• Grantee: Gabriela Di Iorio Leite
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

In its normal conformation, the cellular prion protein (PrPC) exerts innumerable cellular and cognitive functions, among them stand out functions as signaling and auxiliary in memory fixation. It is a protein anchored in the plasma membrane of all cells and highly present in cells of the brain tissue. With all the knowledge acquired regarding its functions in the last 15 years, there are still doubts about its action and mainly about how the molecular interaction of PrPC with the protection - or activation - of neurodegenerative diseases. PrPC can also bind to divalent metals, especially up to 5 copper ions. However, the functional meanings of this metal-protein interaction are still not completely clear. Both fronts that indicate the participation of these metals in the conversion of the isoforms of the prion protein and its pathogenic form, and those that report PrPC as responsible in the process of metal homeostasis, generate conflicts in the current literature regarding the real role of metals in both diseases as in other neurodegenerative diseases. Studying this relationship allow us not only to conclude the role of PrPC in the CNS mediated via transition metals such as copper, iron and zinc, but also to infer if the phenotype observed in prion diseases is a consequence of metal-PrPC interaction failures. This is one of the points that motivate the execution of this project, aiming to contribute with the clarification of the participation of these metals in neurodegeneration processes. This project aims to elucidate the participation of PrPC in protein aggregation with the influence of the removal of specific transition metals during episodes of metal homeostasis breakdown. For this, mouse astrocyte cells will be used wild type (WT) and knockout for PrPC (KO), and specific chelators for copper, iron and zinc will be used, widely studied and characterized by our research group. Changes in the pattern of protein aggregation will be verified, via acrylamide gels and western blotting.