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Göteborgs universitets publikationer

Bioactive polyphenol interactions with beta amyloid: a comparison of binding modelling, effects on fibril and aggregate formation and neuroprotective capacity

Författare och institution:
S. Das (-); Lina Stark (Institutionen för neurovetenskap och fysiologi); I. F. Musgrave (-); T. Pukala (-); S. D. Smid (-)
Publicerad i:
Food & Function, 7 ( 2 ) s. 1138-1146
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
In this study we compared the effects of a diverse set of natural polyphenolics ligands on in silico interactive modelling, in vitro anti-aggregative properties and neuronal toxicity of beta amyloid. The beta amyloid-binding characteristics of optimised structural conformations of polyphenols with ascribed neuroprotective actions including punicalagin, myricetin, luteolin and honokiol were determined in silico. Thioflavin T and transmission electron microscopy were used to assess in vitro inhibitory effects of these polyphenols on A beta(1-42) fibril and aggregation formation. Phaeochromocytoma (PC12) cells were exposed to A beta(1-42), alone and in combination with test concentrations of each polyphenol (100 mu M) and viability measured using MTT assay. A beta(1-42) evoked a concentration-dependent loss of cell viability in PC12 cells, in which all four polyphenols demonstrated significant inhibition of neurotoxicity. While all compounds variably altered the morphology of A beta aggregation, the flavonoids luteolin and myricetin and the lignan honokiol all bound in a similar hydrophobic region of the amyloid pentamer and exerted the most pronounced inhibition of A beta(1-42) aggregation. Each of the polyphenols demonstrated neuroprotective effects in PC12 cells exposed to A beta(1-42), including punicalagin. These findings highlight some structure-activity insights that can be gleaned into the anti-aggregatory properties of bioactive polyphenols based on modelling of their binding to beta-amyloid, but also serve to highlight the more general cellular neuroprotective nature of such compounds.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin
catechol-type flavonoids, alzheimers-disease, in-vitro, thioflavin-t, endocannabinoid system, memory impairment, nuclear factor, mouse model, protein, inhibitors
Postens nummer:
Posten skapad:
2016-03-21 10:02

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