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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 215, FEB 2021.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 19/21143-0 - Amyloid protein aggregates and the relationship between Alzheimer's Disease and type 2 Diabetes investigated by Ru(II) luminescent complexes
• Grantee: Rose Maria Carlos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/00839-1 - Analysis of the structure-toxicity relationship of b-amyloid peptides and neuroprotective effect of luminescent Ru (II) complexes
• Grantee: Rose Maria Carlos
• Support Opportunities: Regular Research Grants