1C12 Study on nucleation reaction of amyloid β peptide induced by ultrasonic cavitation

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  • 1C12 超音波キャビテーションにより誘発されるアミロイドβペプチドの凝集核生成に関する研究

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Amyloid β (Aβ) peptides form needle-like aggregate called amyloid fibril in vivo to cause Alzheimer's disease. The aggregation reaction is mainly divided into nucleation and fibril elongation phases. Nucleation reaction takes long term in the physiological condition. This slowness of the nucleation reaction prevents us from clarifying its aggregation mechanism. Thus, there is no effective treatment for Alzheimer's disease. Recently, formation of amyloid fibril can be drastically accelerated by ultrasonic irradiation for some peptides. The acceleration mechanism, however, remains unclear. Then, we first investigate acoustic-pressure and frequency dependences of the reaction. From our experimental results, it is revealed that the reaction rate constant for aggregation reaction increased by a factor of 〜1000 as the second-harmonics acoustic pressure increases. We also discovered the optimum frequency for aggregation acceleration near 29 kHz. For explaining these results, we propose an aggregation acceleration model based on dual effects of cavitation bubble, 'local condensation' and 'local heating'. Our theoretical model succeeded in reproducing to acoustic pressure and frequency dependences, showing its essential validity.

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