Analysis of the structure-toxicity relationship of b-amyloid peptides and neuroprotective effect of luminescent Ru (II) complexes

• Grant number: 17/00839-1
• Support type: Regular Research Grants
• Duration: April 01, 2017 - March 31, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Rose Maria Carlos
• Grantee: Rose Maria Carlos
• Home Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Assoc. researchers: Manoel de Arcisio Miranda Filho

Abstract

The toxic oligomers of the b-amyloid (bA) peptide generated in the early stages of aggregation are primarily responsible for the synaptic loss of the CNS, causing cognitive changes in Alzheimer's disease (AD) patients. Due to their instability and structural heterogeneity, information on the structure, mechanism, and physiological effects of bA oligomers are not comprehensively known, hence the increased interest in the structure elucidation strategies and in therapies that target the toxic oligomeric species of bA. Recent studies conducted in our laboratories have shown that luminescent complexes of Ru(II), prepared by us, are luminescent probes sensitive to bA oligomeric species. The selectivity and molecular recognition of these complexes by the oligomeric species motivated us to expand our studies and analyze the relationship between the structure and toxicity of bA oligomers. In this project, we intend to investigate in real time the process of aggregation of a series of bA fragments using Ru(II) complexes, identifying the oligomeric species we have been working with by confocal fluorescence microscopy, combined with electron microscopy, circular dichroism, and X-ray spectroscopy. The toxic oligomers and their growth inhibition for the higher order polymer forms and mature fibrils and/or the dissolution of these species will be identified by the incubation of the oligomers in the absence and presence of the Ru(II) complex with hippocampal neural cells followed by cell viability experiments. (AU)

Scientific publications

(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)

MARCHI, RAFAEL C.; SILVA, ELDEVAN S.; SANTOS, JOSENILTON J.; GUILOSKI, IZONETE C.; DE JESUS, HUGO CESAR R.; DE AGUIAR, INARA; KOCK, FLAVIO V. C.; VENANCIO, TIAGO; DA SILVA, MARIA FATIMA G. F.; FERNANDES, JOAO BATISTA; VITAL, MARIA A. B. F.; SOUZA, LEONARDO CASTRO; SILVA DE ASSIS, HELENA C.; SKIBSTED, LEIF H.; CARLOS, ROSE M. Synthesis, Characterization, and Low-Toxicity Study of a Magnesium(II) Complex Containing an Isovanillate Group. ACS OMEGA, v. 5, n. 7, p. 3504-3512, FEB 25 2020. Web of Science Citations: 0.

DE CAMPOS, ISABELE AP. S.; DOS SANTOS, EDJANE R.; SELLANI, TARCISO ALMEIDA; HERBOZO, CAROLINA C. A.; RODRIGUES, ELAINE G.; ROVEDA, ANTONIO C.; PAZIN, WALLANCE M.; ITO, AMANDO S.; SANTANA, VINICIUS T.; NASCIMENTO, OTACIRO R.; CARLOS, ROSE M. Influence of the Medium on the Photochemical and Photophysical Properties of [Ru(phen)(2)(pPDIp)](2+). CHEMPHOTOCHEM, v. 2, n. 8, p. 757-764, AUG 2018. Web of Science Citations: 0.