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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

Texto completo
Autor(es):
Cali, Mariana P. [1] ; Pereira, Lorena M. B. [1] ; Teodoro, Marcio D. [2] ; Sellani, Tarciso A. [3] ; Rodrigues, Elaine G. [3] ; Carlos, Rose M. [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Fed Sao Carlos, Chem Dept, BR-13565905 Sao Carlos, SP - Brazil
[2] Univ Fed Sao Carlos, Phys Dept, BR-13565905 Sao Carlos, SP - Brazil
[3] EPM UNIFESP, Microbiol Immunol & Parasitol Dept, R Botucatu 862, 8 Andar, BR-04023062 Sao Paulo, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Journal of Inorganic Biochemistry; v. 215, FEB 2021.
Citações Web of Science: 0
Resumo

Neurotoxicity of amyloid beta (A beta) species generated in early stages of aggregation has been associated with development of Alzheimer's disease (AD). Consequently, the field of action of compounds that can identify and inhibit the formation of these species has enlarged considerably. This study investigates the effect and influence of the luminescent, water soluble metal complex cis-{[}Ru(phen)2(3,4Apy)(2)](2+) (RuApy, 3,4Apy = 3,4-diaminopyridine, phen = 1,10-phenanthroline) on the aggregation process and toxicity of A beta(1-40) and its A beta(1-28), A beta(11-22) and A beta(29-40) fragments since their early stages. The absence of correlation between the conformations generated by A beta fragments and the full length 1-40 peptide during aggregation and the absence of toxicity of A beta fragments to PC12 cells in all stages of aggregation indicated that the aggregation pathway and toxicity found to the full-length A beta(1-40) depends on specific interactions between the three fragments. The toxicity of A beta(1-40) was dependent on the aggregation step investigated: species generated at the beginning (15 min) of aggregation were toxic, whereas mature (120 min) fibrils were not. The RuApy complex is not toxic to PC12 cells up to 60 mu M, and does not interfere with the aggregation pathway of the A beta fragments, but interferes with the aggregation of A beta(1-40) and protects the PC12 cells, maintaining 100% of cell viability against the toxicity of A beta(1-40) species generated in early stages of aggregation. (AU)

Processo FAPESP: 19/21143-0 - Agregados de proteínas amiloides e a relação entre a Doença de Alzheimer e Diabetes tipo 2 investigada por complexos luminescentes de Ru(II)
Beneficiário:Rose Maria Carlos
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 17/00839-1 - Análise da relação estrutura-toxicidade de peptídeos b-amiloide e efeito neuroprotetivo de complexos de Ru(II) luminescentes
Beneficiário:Rose Maria Carlos
Linha de fomento: Auxílio à Pesquisa - Regular