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The food additive fast green FCF inhibits α-synuclein aggregation, disassembles mature fibrils and protects against amyloid-induced neurotoxicity
- Source :
- Foodfunction. 12(12)
- Publication Year :
- 2021
-
Abstract
- α-Synuclein (α-syn) aggregates into cytotoxic amyloid fibrils, which are recognized as the defining neuropathological feature of Parkinson's disease (PD). Therefore, inhibiting α-syn fibrillogenesis and disrupting the preformed fibrils are both considered attractive strategies to cure PD. We discovered that a safe food additive, fast green FCF, is capable of inhibiting α-synuclein fibrillogenesis and reducing the related cytotoxicity. Thioflavin T fluorescence assays demonstrated that fast green FCF could inhibit the fibrillogenesis α-synuclein. In the presence of 100 μM fast green FCF, amorphous aggregates were formed and observed by atomic force microscopy. Toxicity assays in cell cultures revealed that fast green FCF significantly reduced the cytotoxicity of α-syn. Molecular dynamics simulations revealed the potential mechanism of the interactions between fast green FCF and α-synuclein. Fast green FCF greatly disrupted the α-synuclein pentamer and reduced the β-sheet content by reducing both nonpolar and polar interactions. Furthermore, two binding sites were identified, named region I (Y39-K45) and region II (H50-Q62). Our data reveal that electrostatic interactions, hydrogen bonds, and π–π interactions synergistically contribute to the binding of fast green FCF to the α-synuclein pentamer. These results indicate that fast green FCF is a candidate prototype for the development of drugs against the aggregation of amyloid fibrils in PD.
- Subjects :
- 0301 basic medicine
Amyloid
Pentamer
Cell Survival
Static Electricity
Molecular Dynamics Simulation
Fibril
Protective Agents
PC12 Cells
03 medical and health sciences
chemistry.chemical_compound
Protein Aggregates
0302 clinical medicine
Lissamine Green Dyes
Fast Green FCF
Animals
Benzothiazoles
Binding site
Cytotoxicity
Neurons
Fibrillogenesis
Hydrogen Bonding
Parkinson Disease
General Medicine
nervous system diseases
Rats
030104 developmental biology
nervous system
chemistry
Biophysics
alpha-Synuclein
Thioflavin
Food Additives
Neurotoxicity Syndromes
030217 neurology & neurosurgery
Food Science
Subjects
Details
- ISSN :
- 2042650X
- Volume :
- 12
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Foodfunction
- Accession number :
- edsair.doi.dedup.....51a0c4917f573bf01757f68a7e87949d