Comparison of Aβ (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(2021)

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摘要
Neurotoxicity of amyloid beta (Aβ) 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 Aβ1–40 and its Aβ1–28, Aβ11–22 and Aβ29–40 fragments since their early stages. The absence of correlation between the conformations generated by Aβ fragments and the full length 1–40 peptide during aggregation and the absence of toxicity of Aβ fragments to PC12 cells in all stages of aggregation indicated that the aggregation pathway and toxicity found to the full-length Aβ1–40 depends on specific interactions between the three fragments. The toxicity of Aβ1–40 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 μM, and does not interfere with the aggregation pathway of the Aβ fragments, but interferes with the aggregation of Aβ1–40 and protects the PC12 cells, maintaining 100% of cell viability against the toxicity of Aβ1–40 species generated in early stages of aggregation.
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关键词
Alzheimer's disease,Ruthenium complexes,Luminescent probes,Amyloid Beta,Toxic oligomers,Transmission Electron microscopy
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