Dissociation of ß-Sheet Stacking of Amyloid ß Fibrils by Irradiation of Intense, Short-Pulsed Mid-infrared Laser.

ABSTRACT

Structure of amyloid ß (Aß) fibrils is rigidly stacked by ß-sheet conformation, and the fibril state of Aß is profoundly related to pathogenesis of Alzheimer's disease (AD). Although mid-infrared light has been used for various biological researches, it has not yet been known whether the infrared light changes the fibril structure of Aß. In this study, we tested the effect of irradiation of intense mid-infrared light from a free-electron laser (FEL) targeting the amide bond on the reduction of ß-sheet content in Aß fibrils. The FEL reduced entire contents of proteins exhibiting ß-sheet structure in brain sections from AD model mice, as shown by synchrotron-radiation infrared microscopy analysis. Since Aß1-42 fibril absorbed a considerable FEL energy at amide I band (6.17 µm), we irradiated the FEL at 6.17 µm and found that ß-sheet content of naked Aß1-42 fibril was decreased using infrared microscopic analysis. Consistent with the decrease in the ß-sheet content, Congo-red signal is decreased after the irradiation to Aß1-42 fibril. Furthermore, electron microscopy analysis revealed that morphologies of the fibril and proto-fibril were largely changed after the irradiation. Thus, mid-infrared light dissociates ß-sheet structure of Aß fibrils, which justifies exploration of possible laser-based therapy for AD.