Thioflavin T Promotes Aβ(1–40) Amyloid Fibrils Formation

Abstract

Fibrillogenesis of the small peptide Aβ(1-40) is considered to be the hallmark of Alzheimer's disease. Some evidence indicates small oligomers, rather than mature fibrils, as the key cytotoxic agents. The fluorescent dye Thioflavin T (ThT) is often used to detect amyloid deposits in both in vivo and in vitro experiments, and it is used to study kinetic measurements, under the fundamental hypothesis that this probe does not influence the aggregation processes. We report experimental data showing that ThT may promote the Aβ(1-40) peptide amyloid aggregation changing solvent-peptide interactions and stabilizing more ordered β-like conformation. This finding has a two-fold importance: It is a fundamental warning in all fibrillation experiments where ThT is used as fluorescent probe, and it suggests that ThT, accelerating fibril formation, could be used to reduce the presence of transient small oligomers, thus interfering with the pathogenic impact of Aβ peptide.

The Chlamydia pneumoniae Adhesin Pmp21 Forms Oligomers with Adhesive Properties

“…However, dimer formation has also been observed for amyloid-like proteins upon sample preparation for SDS-PAGE (55). Moreover, in vitro ThT-induced amyloid aggregation has been described, and this might also contribute to the formation of oligomeric D-Wt (56).…”

Torsional Dynamics of Thioflavin T in Room‐Temperature Ionic Liquids: An Effect of Heterogeneity of the Medium

“…The angular mobility is given by the Einstein relationship, which is quite close to that of the equation of translational mobility of charged particles [Eq. (19)]:…”

“…[6][7][8][9][10][11][12][13][14] Nath et al used the femtosecond fluorescence upconversion technique to observe the effect of viscosity on the dynamics of excited-state relaxation in different solvents and concluded the formation of a new, twisted, emissive excited state. [14] Several groups have studied the nature of the binding of ThT with amyloid fibrils [15][16][17][18][19] by using fluorescence and absorption spectroscopy. [20][21][22] Huppert et al [23] developed a computational model to explain the time-dependent emission spectra of ThT and experimentally studied the emission properties of ThT adsorbed and immobilised inside oxidised porous silicon with an enhanced fluorescence decay time.…”

Supramolecular Inhibition of Amyloid Fibrillation by Cucurbit[7]uril

“…An ex situ ThT assay was used to prevent ThT from influencing the fibrillation kinetics. [12] CB [7] successfully inhibited fibrillation at Ins:CB [7] ratios of 1:0.5 or with a higher ratio of CB [7] to Ins as suggested by the fact that there was little or no change in the ThT fluorescence intensity. No trace of amyloid fibrils was observed in the TEM images of Ins with CB [7] after a 42 h incubation, except at a ratio of 1:0.5 (Figure 1 c).…”