[2P01-53] Poster Presentation

[2P51] The role of curcumin tautomerization in the disassembly of pentameric amyloid β42 oligomers

Atsuya Matsui¹, Jean Pierre Bellier², *Koutaro Fujii¹, Takafumi Ishibe³, Yoshiaki Nakamura³, Hiroyasu Taguchi⁴, Nobuyasu Naruse¹, Yutaka Mera¹ (1. Department of Fundamental Bioscience, Shiga University of Medical Science, 2. Department, Brigham and Women’s Hospital, 3. Graduate School of Engineering Science, Osaka University, 4. Kyoto Womens’ University)

Alzheimer’s disease is characterized by amyloid-β peptide (Aβ) accumulation, initiating neurodegeneration. Pathogenic Aβ42 oligomers (oAβ42) drive the disease, emphasizing the significance of their investigation. Atomic force microscopic imaging revealed that curcumin and its derivatives with tautomerization play a role in disassembling oAβ42, in contrast to control derivatives that lack tautomerization. Molecular dynamics simulations supported our experimental findings. When curcumin and its derivatives with tautomerism bind to the hydrophobic region of oAβ42, the keto-form changes to the enol-form. This transformation causes conformational changes, leading to shifts in potential energy. Tautomerism allows curcumin to act as a torsional molecular spring, ultimately pulling apart the intermolecular space of the pentameric oAβ42.