Original articleTrehalose induced conformational changes in the amyloid-β peptide

- Amyloid-β (Aβ) peptide appears to possess little helical structure in dilute aqueous solutions.
- The formation of pathological amyloid deposits is accompanied by conformational changes of the soluble Aβ peptide into β-sheet structures.
- We show that in the presence of a natural compound, trehalose, Aβ peptide adopts more helical content and undergoes a disorder/order conformational transition.
- Our studies may provide a mechanism by which trehalose reduces Aβ deposits and improved cognitive functions in transgenic mice as reported in earlier studies.

Alzheimer's disease is an irreversible and progressive brain disorder featured by the accumulation of Amyloid-β (Aβ) peptide, which forms insoluble assemblies that builds up into plaques resulting in cognitive decline and memory loss. The formation of fibrillar amyloid deposits is accompanied by conformational changes of the soluble Aβ peptide into β-sheet structures. Strategies to prevent or reduce Aβ aggregation using small molecules such as trehalose have shown beneficial effects under in vitro cell- and in vivo mouse- models. However, the role of trehalose in reducing Aβ peptide aggregation is still not clear. In the present study, using circular dichroism- and fluorescence emission- spectroscopies, we demonstrated that in the presence of trehalose, Aβ peptide adopts more helical content and undergoes a disorder/order conformational transition. Based on our findings, we conclude that trehalose affects the conformation of Aβ peptide to form α-helical structure, which may inhibit the formation of β-sheets and thereby aggregation.