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Temperature dependence of Congo red binding to amyloid β12-28
Ruel E McKnight1, Douglas R Jackson, Kazushige Yokoyama
1Department of Chemistry, State University of New York, College at Geneseo, Geneseo, NY, 14454, USA. mcknight@geneseo.edu
European Biophysics Journal : EBJ
|May 3, 2013
Summary
Congo red (CR) binding to amyloid beta (Aβ) decreases with increasing temperature, hindering its therapeutic potential for Alzheimer's disease. However, CR disaggregation occurs at higher temperatures, offering alternative mechanisms for inhibiting Aβ toxicity.
Area of Science:
- Biochemistry
- Neuroscience
- Pharmacology
Background:
- Congo red (CR) shows potential therapeutic applications for neurodegenerative diseases like Alzheimer's due to its ability to bind amyloid beta (Aβ) intermediates.
- Understanding the precise interaction between CR and Aβ is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the temperature-dependent interaction between Congo red and the Aβ(12-28) peptide.
- To elucidate the thermodynamic and kinetic parameters governing CR-Aβ(12-28) complexation and disaggregation.
Main Methods:
- Isothermal titration calorimetry (ITC) was employed to study the binding of CR to Aβ(12-28) across a temperature range of 15-35 °C.
Main Results:
- CR binding to Aβ(12-28) significantly decreased with increasing temperature, with no binding observed at 35 °C, likely due to conformational changes in Aβ(12-28).
- Binding was characterized by favorable enthalpy and entropy changes, yielding binding constants (K) between 10(5) and 10(6) M⁻¹.
- An initial, entropy-driven CR disaggregation phase (K ~10(7)-10(8) M⁻¹) preceded complexation, and only disaggregation was observed at 35 °C.
Conclusions:
- Temperature critically influences the interaction between CR and Aβ(12-28), impacting its potential as a therapeutic agent.
- The findings suggest that CR's ability to inhibit Aβ toxicity may involve mechanisms beyond direct complexation, such as disaggregation, especially at elevated temperatures.
