Gallic acid interacts with α-synuclein to prevent the structural collapse necessary for its aggregation.
The accumulation of protein aggregates containing amyloid fibrils, with α-synuclein being the main component, is a pathological hallmark of Parkinson's disease (PD). Molecules which prevent the formation of amyloid fibrils or disassociate the toxic aggregates are touted as promising strategies to prevent or treat PD. In the present study, in vitro Thioflavin T fluorescence assays and transmission electron microscopy imaging results showed that gallic acid (GA) potently inhibits the formation of amyloid fibrils by α-synuclein. Ion mobility-mass spectrometry demonstrated that GA stabilises the extended, native structure of α-synuclein, whilst NMR spectroscopy revealed that GA interacts with α-synuclein transiently.
School of Chemistry and Physics, The University of Adelaide, Adelaide SA 5005, Australia.
Yanqin
Y
Liu
Research School of Chemistry, The Australian National University, Canberra ACT 0200, Australia.
John A
JA
Carver
School of Chemistry and Physics, The University of Adelaide, Adelaide SA 5005, Australia.
Antonio N
AN
Calabrese
School of Chemistry and Physics, The University of Adelaide, Adelaide SA 5005, Australia. Electronic address: tara.pukala@adelaide.edu.au.
Tara L
TL
Pukala
D000682:Amyloid / Q000037:antagonists & inhibitors / Q000737:chemistry*; D052160:Benzothiazoles; D005427:Flocculation; D005456:Fluorescent Dyes; D005707:Gallic Acid / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013844:Thiazoles; D051844:alpha-Synuclein / Q000737:chemistry*
D000682:Amyloid; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D011994:Recombinant Proteins; D013844:Thiazoles; D051844:alpha-Synuclein; C009462:thioflavin T; D005707:Gallic Acid
Amyloid fibril; Gallic acid; Ion mobility mass spectrometry; NMR spectroscopy; α-Synuclein