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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.
- Source :
-
Journal of inorganic biochemistry [J Inorg Biochem] 2021 Feb; Vol. 215, pp. 111314. Date of Electronic Publication: 2020 Nov 21. - Publication Year :
- 2021
-
Abstract
- 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) <subscript>2</subscript> (3,4Apy) <subscript>2</subscript> ] <superscript>2+</superscript> (RuApy, 3,4Apy = 3,4-diaminopyridine, phen = 1,10-phenanthroline) on the aggregation process and toxicity of Aβ <subscript>1-40</subscript> and its Aβ <subscript>1-28</subscript> , Aβ <subscript>11-22</subscript> and Aβ <subscript>29-40</subscript> 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 Aβ <subscript>1-40</subscript> depends on specific interactions between the three fragments. The toxicity of Aβ <subscript>1-40</subscript> 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 Aβ <subscript>1-40</subscript> and protects the PC12 cells, maintaining 100% of cell viability against the toxicity of Aβ <subscript>1-40</subscript> species generated in early stages of aggregation.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Alzheimer Disease pathology
Amyloid beta-Peptides drug effects
Animals
Cell Survival drug effects
Coordination Complexes chemistry
Microscopy, Electron, Transmission
PC12 Cells
Peptide Fragments drug effects
Peptide Fragments metabolism
Protein Aggregation, Pathological pathology
Rats
Ruthenium chemistry
Solubility
Water chemistry
Alzheimer Disease metabolism
Amyloid beta-Peptides metabolism
Coordination Complexes pharmacology
Protein Aggregation, Pathological metabolism
Ruthenium pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3344
- Volume :
- 215
- Database :
- MEDLINE
- Journal :
- Journal of inorganic biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33261934
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2020.111314