6 research outputs found
'Click' assembly of glycoclusters and discovery of a trehalose analogue that retards A(beta)40 aggregation and inhibits A(beta)40-induced neurotoxicity
Osmolytes have been proposed as treatments for neurodegenerative proteinopathies including Alzheimer's disease. However, for osmolytes to reach the clinic their efficacy must be improved. In this work, copper(I)-catalyzed azide-alkyne cycloaddition chemistry was used to synthesize glycoclusters bearing six copies of trehalose, lactose, galactose or glucose, with the aim of improving the potency of these osmolytes via multivalency. A trehalose glycocluster was found to be superior to monomeric trehalose in its ability to retard the formation of amyloid-beta peptide 40 (Aβ40) fibrils and protect neurons from Aβ40-induced cell death
Facile synthesis of surface modified poly-(L-lysine)dendrimers by solid phase peptide synthesis
Metal chelation, radical scavenging and inhibition of Aβ42 fibrillation by food constituents in relation to Alzheimer's disease
Various food constituents have been proposed as disease-modifying agents for Alzheimer'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 (A beta). In this study, nine different food constituents (L-ascorbic acid, caffeic acid, caffeine, curcumin, (-)-epigallocatechin gallate (EGCG), gallic acid, propyl gallate, resveratrol, and alpha-tocopherol) were investigated for their effects on the above factors, using metal chelation assays, antioxidant assays, and assays of A beta(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 alpha-tocopherol, with better brain uptake, deserve further investigation for specifically addressing oxidative stress within the AD brain. (c) 2015 Elsevier Ltd. All rights reserved