Studies for Prion Protein Cellular and metallic ions in oxidative stress

• Grant number: 18/14152-0
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2019 - April 30, 2021
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Giselle Cerchiaro
• Grantee: Giselle Cerchiaro
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated scholarship(s): 19/22597-5 - Technical training in cell culture, BP.TT; 18/26838-4 - Maintenance and experimentation in cell culture, BP.TT

Abstract

In its normal conformation, the cellular prion protein (PrPC) exerts innumerable cellular and cognitive functions; among them we detach functions as signaling platform 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 and concerns 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 with up to 5 copper ions. However, the functional meanings of this metal-protein interaction are still not completely clear. There are studies 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 co-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 allows us not only to conclude the role of PrPC in the CNS mediated via Fe, Cu, Zn and/or Mn, but also to infer if the phenotype observed in prion diseases is a consequence of failures in the metal-PrPC interaction. This is one of the points that motivate us in this work, aiming to contribute with the clarification of the participation of these metals in neurodegeneration processes.This project has the main to elucidate the participation of PrPC in the internalization of metals during episodes of oxidative stress and in induction of cellular neurodegeneration. For this, mouse astrocyte cells will be used: wild type (WT) and knockout for PrPC (KO), and levels of copper, iron and zinc metals internalized in the presence and absence of oxidative stress and in neurodegeneration will be measured. In addition, changes in the expression and localization of the SOD1 (superoxide dismutase) enzyme under these conditions will be verified, as well as proteins involved with cell death as the caspases, and their relations with PrPC. With these results it will be possible to create a clear link between PrPC, its action on the pathways of death and the molecular involvement of transition metals in this process. (AU)

Scientific publications

(4)

(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)

MARQUES, CAROLINE M. S.; PEDRON, TATIANA; BATISTA, BRUNO L.; CERCHIARO, GISELLE. Cellular prion protein activates Caspase 3 for apoptotic defense mechanism in astrocytes. Molecular and Cellular Biochemistry, v. 476, n. 5, FEB 2021. (18/14152-0)

MANIERI, TANIA M.; SENSI, STEFANO L.; SQUITTI, ROSANNA; CERCHIARO, GISELLE. Structural effects of stabilization and complexation of a zinc-deficient superoxide dismutase. HELIYON, v. 7, n. 1, JAN 2021. (12/24604-0, 18/14152-0)

MAMUD, JULIA F.; BIAZOLLA, GIOVANNA; MARQUES, CAROLINE S.; CERCHIARO, GISELLE; DE QUEIROZ, THIAGO B.; KEPPLER, ARTUR F.; POLO, ANDRE S.. Z to E light-activated isomerization of alpha-pyridyl-N-arylnitrone ligands sensitized by rhenium(I) polypyridyl complexes. Inorganica Chimica Acta, v. 514, JAN 1 2021. (16/21993-6, 18/14152-0, 12/07717-5, 15/20007-5, 17/07289-7)

RAMOS, LUIZ D.; DE MACEDO, LEONARDO H.; GOBO, NICHOLAS R. S.; DE OLIVEIRA, KLEBER T.; CERCHIARO, GISELLE; MORELLI FRIN, KARINA P.. Understanding the photophysical properties of rhenium(I) compounds coordinated to 4,7-diamine-1,10-phenanthroline: synthetic, luminescence and biological studies. DALTON TRANSACTIONS, v. 49, n. 45, p. 16154-16165, DEC 7 2020. (18/14152-0, 18/00106-7, 17/18063-0, 16/09652-9)

Filed patent(s) as a result of this research project