Thioflavin T templates amyloid β(1-40) conformation and aggregation pathway

Area of Science:

• Biochemistry
• Neuroscience
• Molecular Biology

Background:

• Alzheimer's disease (AD) is linked to amyloid-beta (Aβ) peptide aggregation.
• Understanding Aβ(1-40) assembly is crucial for developing AD therapies.
• Fluorescent probes like Thioflavin T (ThT) are widely used to monitor amyloid formation.

Purpose of the Study:

• To investigate the impact of Thioflavin T (ThT) on Aβ(1-40) conformation, stability, and aggregation.
• To elucidate the molecular mechanisms by which ThT influences Aβ(1-40) self-assembly.
• To assess the reliability of ThT as a probe in amyloid research.

Main Methods:

• Experimental techniques combined with Molecular Dynamics (MD) simulations.
• Analysis of Aβ(1-40) peptide conformation and stability in the presence of ThT.
• Investigating ThT-induced changes in supramolecular assembly and aggregation pathways.

Main Results:

• Thioflavin T (ThT) alters Aβ(1-40) peptide conformation, inducing a rigid, partially-folded state.
• ThT promotes specific supramolecular associations that enhance aggregation propensity.
• The presence of ThT shifts the equilibrium towards aggregation-prone peptide species.

Conclusions:

• ThT is not an inert probe and can artifactually accelerate Aβ(1-40) aggregation.
• Findings suggest strategies to control or block Aβ aggregation by manipulating peptide conformation.
• Emphasizes the critical need for label-free techniques for unbiased studies of Aβ aggregation.