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

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)

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Scientific publications (5)
(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)
PEREIRA, LORENA M. B.; CALI, MARIANA P.; MARCHI, RAFAEL C.; PAZIN, WALLANCE M.; CARLOS, ROSE M.. Luminescent imaging of insulin amyloid aggregation using a sensitive ruthenium-based probe in the red region. Journal of Inorganic Biochemistry, v. 224, . (20/12129-1, 19/21143-0, 17/00839-1)
SILVA, ELDEVAN; MARCHI, RAFAEL; MATOS, CARLA; SILVA, MARIA; FERNANDES, JOAO; BUENO, ODAIR; CARLOS, ROSE. INSECTICIDAL AND FUNGICIDAL ACTIVITY OF A MAGNESIUM COMPOUND CONTAINING ISOVANILLIC ACID AGAINST LEAF-CUTTING ANT AND ITS SYMBIOTIC FUNGUS. Química Nova, v. 44, n. 3, p. 267-271, . (18/16040-5, 13/05536-6, 17/00839-1, 18/09145-5, 15/23146-6, 17/15455-4, 19/21143-0)
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.; et al. Influence of the Medium on the Photochemical and Photophysical Properties of [Ru(phen)(2)(pPDIp)](2+). CHEMPHOTOCHEM, v. 2, n. 8, p. 757-764, . (17/00839-1, 16/09633-4)
CALI, MARIANA P.; PEREIRA, LORENA M. B.; TEODORO, MARCIO D.; SELLANI, TARCISO A.; RODRIGUES, ELAINE G.; CARLOS, ROSE M.. Comparison of A beta (1-40, 1-28, 11-22, and 29-40) aggregation processes and inhibition of toxic species generated in early stages of aggregation by a water-soluble ruthenium complex. Journal of Inorganic Biochemistry, v. 215, . (19/21143-0, 17/00839-1)
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; et al. Synthesis, Characterization, and Low-Toxicity Study of a Magnesium(II) Complex Containing an Isovanillate Group. ACS OMEGA, v. 5, n. 7, p. 3504-3512, . (18/09145-5, 13/05536-6, 17/00839-1, 15/23146-6, 18/16040-5, 17/15455-4)

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