Molecular mechanism of tau aggregation induced by anionic and cationic dyes
| Autor: | Karla I Lira-De León, Victoria Campos-Peña, Iris N. Serratos, Marco Antonio Meraz-Ríos, M.D.P. Figueroa-Corona, Marianela Palomera-Cárdenas, Ponciano García-Gutiérrez |
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| Rok vydání: | 2013 |
| Předmět: |
Anions
Models Molecular Tau protein tau Proteins Protein Structure Secondary Cell Line chemistry.chemical_compound Protein structure Thiazine Cations mental disorders Electrochemistry Humans Benzothiazoles Binding site Organic Chemicals Coloring Agents biology General Neuroscience Lysine Congo Red General Medicine Flow Cytometry Immunohistochemistry Congo red Methylene Blue Psychiatry and Mental health Clinical Psychology Microscopy Electron Thiazoles chemistry Solubility Docking (molecular) Biophysics biology.protein Thermodynamics Thioflavin Geriatrics and Gerontology Methylene blue Protein Binding |
| Zdroj: | Journal of Alzheimer's disease : JAD. 35(2) |
| ISSN: | 1875-8908 |
| Popis: | Abnormal tau filaments are a hallmark of Alzheimer's disease. Anionic dyes such as Congo Red, Thiazine Red, and Thioflavin S are able to induce tau fibrillization in vitro. SH-SY5Y cells were incubated with each dye for seven days leading to intracellular aggregates of tau protein, with different morphological characteristics. Interestingly, these tau aggregates were not observed when the Methylene Blue dye was added to the cell culture. In order to investigate the molecular mechanisms underlying this phenomenon, we developed a computational model for the interaction of the tau paired helical filament (PHF) core with every dye by docking analysis. The polar/electrostatic and nonpolar contribution to the free binding energy in the tau PHF core-anionic dye interaction was determined. We found that the tau PHF core can generate a positive net charge within the binding site localized at residuesLys311 and Lys340 (numbering according to the longest isoform hTau40). These residues are important for the binding affinity of the negative charges present in the anionic dyes causing an electrostatic environment that stabilizes the complex. Tau PHF core protofibril-Congo Red interaction has a stronger binding affinity compared to Thiazine Red or Thioflavin S. By contrast, the cationic dye Methylene Blue does not bind to nor stabilize the tau PHF core protofibrils. These results characterize the driving forces responsible for the binding of tau to anionic dyes leading to their self-aggregation and suggest that Methylene Blue may act as a destabilizing agent of tau aggregates. |
| Databáze: | OpenAIRE |
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