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

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Abstract

Structure of amyloid β (Aβ) fibrils is rigidly stacked by β-sheet conformation, and the fibril state of Aβ 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 Aβ. 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 β-sheet content in Aβ fibrils. The FEL reduced entire contents of proteins exhibiting β-sheet structure in brain sections from AD model mice, as shown by synchrotron-radiation infrared microscopy analysis. Since Aβ1-42 fibril absorbed a considerable FEL energy at amide I band (6.17 μm), we irradiated the FEL at 6.17 μm and found that β-sheet content of naked Aβ1-42 fibril was decreased using infrared microscopic analysis. Consistent with the decrease in the β-sheet content, Congo-red signal is decreased after the irradiation to Aβ1-42 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 β-sheet structure of Aβ fibrils, which justifies exploration of possible laser-based therapy for AD.

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Abbreviations

Aβ:

Amyloid beta

AD:

Alzheimer’s disease

AICD:

APP intracellular domain

APP:

Amyloid precursor protein

FEL:

Free-electron laser

PS1:

Presenilin 1

sAPPβ:

Secreted amyloid precursor protein-β

YAG:

Yttrium aluminum garnet

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Acknowledgements

We thank Dr. Kanjiro Torigoe (Graduate School of Science and Technology, Tokyo University of Science) for technical support of TEM analyses. We also thank Dr. Takayuki Imai (FEL-TUS), Mr. Tetsuo Morotomi, and Mr. Keiichi Hisazumi (MITSUBISHI ELECTRIC SYSTEM & SERVICE CO., LTD.) for operating the FEL instrument. This work was supported by the Open Advanced Research Facilities Initiative and the Photon Beam Platform Project of the Ministry of Education, Culture, Sport, Science and Technology, Japan (to T. K., T. O., and K. T.), JSPS KAKENHI Grant Number JP16K15553 (to K. N.), and grants from SENSHIN Medical Research Foundation (to K. N.) and Takeda Science Foundation (to K. N.).

Funding

T.K. and K.N. set up the hypothesis. T.K., T.O., K.T., and K.N. designed the experiments. T.K., T.Y., and K.N. performed experiments and analyzed the data. T.K., K.T., and K.N. wrote the manuscript.

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Correspondence to Takayasu Kawasaki or Kazuhiro Nakamura.

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Kawasaki, T., Yaji, T., Ohta, T. et al. Dissociation of β-Sheet Stacking of Amyloid β Fibrils by Irradiation of Intense, Short-Pulsed Mid-infrared Laser. Cell Mol Neurobiol 38, 1039–1049 (2018). https://doi.org/10.1007/s10571-018-0575-8

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