DMSO affects Aβ_1–40's conformation and interactions with aggregation inhibitors as revealed by NMR

Abstract

DMSO alters Abeta's conformation and its recognition by inhibitors.

The Effect of Ethanol on Disassembly of Amyloid-β1-42 Pentamer Revealed by Atomic Force Microscopy and Gel Electrophoresis

“…Several alcohols have been shown to effectively disassemble Aβ 1-42 oligomeric assemblies by acting on the tertiary and quaternary structures, although the exact molecular mechanism remains unknown [13,19,20]. Other studies have reported the effect of another solvent, dimethyl sulfoxide (DMSO), on the conformation of Aβ 1-40 and Aβ 1-42 [21,22]. However, the effect of ethanol on already assembled Aβ 1-42 oligomers has never been reported, even if ethanol has been shown to prevent Aβ aggregation and protect cultured cells against both Aβ-induced cell death and synapse damage [23,24].…”

A pyrene-inhibitor fluorescent probe with large Stokes shift for the staining of Aβ1–42, α-synuclein, and amylin amyloid fibrils as well as amyloid-containing Staphylococcus aureus biofilms

“…We have chosen Compound 1 (Chart 1) as the scaffold for the design and synthesis of Aβ fluorescent markers because it is the more water soluble [17] and less cytotoxic of the amyloid aggregation inhibitors previously described [16]. The fluorescent dye pyrene has been selected to label Compound 1 because of its high fluorescence quantum yield.…”

“…1-pyrenemethylamine has been used as reactant in the coupling reaction because it allows a fine control of its chemical reactivity. While the residues of Aβ1-40 that interact with Compound 1 have been determined [17], the atoms of Compound 1 that are engaged in the interaction are not known. Therefore, we have synthesized 4 derivatives of Compound 1 (Compounds 1A, 1B, 1C and 1D) having the fluorescent dye located in different positions or joined with linkers of different length (Chart 1) hoping to retain the amyloid binding properties in at least some of them.…”

“…By adapting high throughput experimental screening methods previously used to discover pharmacological chaperones [14] and protein inhibitors [15], we reported the discovery of four compounds that inhibit the aggregation of Aβ17-40 and Aβ1-42 both in vitro and in fungi models [16]. As those compounds interact with Aβ aggregating species [17] suitable fluorescent derivatives could be used to detect and quantitate Aβ fibrils by means of fluorescence microscopy. Thioflavin T (ThT) is at present the fluorescent probe most commonly used to stain amyloid fibrils and to follow the aggregation kinetics of amyloidogenic proteins [18].…”

Complex System Assembly Underlies a Two-Tiered Model of Highly Delocalized Electrons

“…21 After 1 or 7 days of incubation, the ability of the samples to enhance ThT fluorescence was measured and compared to that of parent samples in water. Whereas DMSO is an appropriate solvent to maintain Aβ monomeric, 22 once the fibrils are wellformed and have reached the maximum cooperative effects, they are more resistant to disruptive effect of 100% DMSO than the Q/N-rich system, which readily dissociates after 1 day (Figure 4B). This is in line with previous observations on the hydrophobic α-synuclein amyloid fibrils 23 and supports the special role of Gln and Asn side chains in the highly efficient assembly of the polar oligomer.…”