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Inhibition and disaggregation of α-synuclein oligomers by natural polyphenolic compounds
- Source :
- FEBS Letters. (8):1113-1120
- Publisher :
- Federation of European Biochemical Societies. Published by Elsevier B.V.
-
Abstract
- Aggregation of alpha-synuclein (αS) into oligomers is critically involved in the pathogenesis of Parkinson’s disease (PD). Using confocal single-molecule fluorescence spectroscopy, we have studied the effects of 14 naturally-occurring polyphenolic compounds and black tea extract on αS oligomer formation. We found that a selected group of polyphenols exhibited potent dose-dependent inhibitory activity on αS aggregation. Moreover, they were also capable of robustly disaggregating pre-formed αS oligomers. Based upon structure–activity analysis, we propose that the key molecular scaffold most effective in inhibiting and destabilizing self-assembly by αS requires: (i) aromatic elements for binding to the αS monomer/oligomer and (ii) vicinal hydroxyl groups present on a single phenyl ring. These findings may guide the design of novel therapeutic drugs in PD.Structured summary of protein interactionsAlpha-synuclein binds to Alpha-synuclein by biophysical (View Interaction 1, 2)
- Subjects :
- Polyphenol
Stereochemistry
Biophysics
Ascorbic Acid
Morin
Deferoxamine
Iron Chelating Agents
Biochemistry
Oligomer
Antioxidants
Alpha-synuclein
Structure-Activity Relationship
chemistry.chemical_compound
Aggregation
Protein structure
Phenols
Structural Biology
Genetics
Humans
Structure–activity relationship
Apigenin
Protein Structure, Quaternary
Molecular Biology
Confocal fluorescence spectroscopy
Flavonoids
Microscopy, Confocal
Dose-Response Relationship, Drug
Molecular Structure
Polyphenols
Parkinson Disease
Cell Biology
Aromatic interaction
Recombinant Proteins
Acetylcysteine
Spectrometry, Fluorescence
Monomer
Microscopy, Fluorescence
chemistry
Flavanones
Mutation
Parkinson’s disease
Myricetin
Protein Multimerization
Subjects
Details
- Language :
- English
- ISSN :
- 00145793
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- FEBS Letters
- Accession number :
- edsair.doi.dedup.....c1777d0a5627adcbd6dd41cf02f14c7b
- Full Text :
- https://doi.org/10.1016/j.febslet.2011.03.046