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6-gingerol interferes with amyloid-beta (Aβ) peptide aggregation

Berntsson, E.; Paul, S.; Sholts, S. B.; Jarvet, J.; Barth, A.; Graslund, A.; Warmlander, S. K. T. S.

2021-01-04 biochemistry
10.1101/2021.01.03.425159 bioRxiv
Show abstract

Alzheimers disease (AD) is the most prevalent age-related cause of dementia. AD affects millions of people worldwide, and to date there is no cure. The pathological hallmark of AD brains is deposition of amyloid plaques, which mainly consist of amyloid-{beta} (A{beta}) peptides, commonly 40 or 42 residues long, that have aggregated into amyloid fibrils. Intermediate aggregates in the form of soluble A{beta} oligomers appear to be highly neurotoxic. Cell and animal studies have previously demonstrated positive effects of the molecule 6-gingerol on AD pathology. Gingerols are the main active constituents of the ginger root, which in many cultures is a traditional nutritional supplement for memory enhancement. Here, we use biophysical experiments to characterize in vitro interactions between 6-gingerol and A{beta}40 peptides. Our experiments with atomic force microscopy imaging, and nuclear magnetic resonance and Thioflavin-T fluorescence spectroscopy, show that the hydrophobic 6-gingerol molecule interferes with formation of A{beta}40 aggregates, but does not interact with A{beta}40 monomers. Thus, together with its favourable toxicity profile, 6-gingerol appears to display many of the desired properties of an anti-AD compound.

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