Metal chelation, radical scavenging and inhibition of Aβ42 fibrillation by food constituents in relation to Alzheimer’s disease

Abstract

, Metal chelation, radical scavenging and inhibition of Aβ 42-fibrillation by food constituents in relation to Alzheimer's disease, Food Chemistry (2015), doi: http://dx.doi.org/10.1016/j.foodchem. 2015.11.118 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 These authors contributed equally to this work. Metal chelation, radical scavenging and inhibition of Aβ Abstract Various food constituents have been proposed as disease-modifying agents forAlzheimer's Disease (AD), due to epidemiological evidence of their beneficial effects, and for their ability to ameliorate factors linked to AD pathogenesis, namely by: chelating iron, copper and zinc; scavenging reactive oxygen species; and suppressing the fibrillation of amyloid-beta peptide (Aβ). In this study, nine different food constituents (L-ascorbic acid, caffeic acid, caffeine, curcumin, (−)-epigallocatechin gallate (EGCG), gallic acid, propyl gallate, resveratrol, and α-tocopherol) were investigated for their effects on the above factors, using metal chelation assays, antioxidant assays, and assays of Aβ 42 fibrillation. An assay method was developed using 5-Br-PAPS to examine the complexation of Zn(II) and Cu(II).EGCG, gallic acid, and curcumin were identified as a multifunctional compounds, however their poor brain uptake might limit their therapeutic effects. The antioxidants L-ascorbic acid and α-tocopherol, with better brain uptake, deserve further investigation for specifically addressing oxidative stress within the AD brain.

β-Hairpin mimics containing a piperidine–pyrrolidine scaffold modulate the β-amyloid aggregation process preserving the monomer species

“…Resveratrol exhibits multi-target activity and thus is not selective for Aβ 1–42 aggregation. For example, resveratrol inhibits similarly the aggregation of other amyloid proteins such as IAPP 36 (EGCG also inhibits similarly Aβ 1–42 and IAPP aggregation in ThT fluorescence assays 37,38 ), which is not the case for G1b and G2b , as mentioned above. By choosing the SREs in our β-hairpin mimics, specifically according to the target amyloid proteins, we can modulate the activity and expect selective activities.…”

Oxidized epigallocatechin gallate inhibited lysozyme fibrillation more strongly than the native form

“…Under the experimental conditions of this study, 50% EGCG degrades in less than 2 h. Two main oxidation products have been detected by mass spectrometry. Gallic acid, corresponding to the ion at m/z 169, has been reported to inhibit amyloid formation of proteins with lower activity than EGCG [37], [38], [39]. The [M–H] – ion at m/z 225 is rarely reported.…”

Docking Studies and Biological Evaluation of a Potential β-Secretase Inhibitor of 3-Hydroxyhericenone F from Hericium erinaceus

“…Various food constituents have been proposed as disease-modifying agents for AD, due to epidemiological evidence of their beneficial effects, and due to their ability to ameliorate the factors that are associated with the pathogenesis of AD pathogenesis (Chan et al, 2016). Such constituents have been demonstrated to bind iron, copper and zinc, scavenge reactive oxygen species and suppress the fibrillation of amyloid-beta peptide (Aβ), thus contributing to the prevention of AD (Chan et al, 2016).…”