学術雑誌論文

学術雑誌論文

text

Journal of Biological Chemistry. 2015, 290(2), p. 815-826

Small Liposomes Accelerate the Fibrillation of Amyloid β (1–40)

American Society for Biochemistry and Molecular Biology

英語

text

2015-01

https://doi.org/10.1074/jbc.M114.592527

This research was originally published in the Journal of Biological Chemistry. Mayu S. Terakawa, Hisashi Yagi, Masayuki Adachi, Young-Ho Lee and Yuji Goto. Small Liposomes Accelerate the Fibrillation of Amyloid β (1–40). J. Biol. Chem. 2015; 290, 815-826. © the American Society for Biochemistry and Molecular Biology

The deposition of amyloid β (Aβ) peptides is a pathological hallmark of Alzheimer disease. Aβ peptides were previously considered to interact specifically with ganglioside-containing membranes. Several studies have suggested that Aβ peptides also bind to phosphatidylcholine membranes, which lead to deformation of membranes and fibrillation of Aβ. Moreover, the role of membrane curvature, one type of deformation produced by binding of proteins to a membrane, in the binding and fibrillation of Aβ remains unclear. To clearly understand the relationship between the binding, consequent membrane deformation, and fibrillation of Aβ, we examined the amyloid fibrillation of Aβ-(1–40) in the presence of liposomes of various sizes. Membrane curvature increased with a decrease in the size of the liposomes. We used liposomes made of 1,2-dioleoyl-sn-glycero-3-phosphocholine to eliminate electrostatic effects. The results obtained showed that liposomes of smaller sizes (≤50 nm) significantly accelerated the nucleation step, thereby shortening the lag time of fibrillation. On the other hand, liposomes of larger sizes decreased the amount of fibrils but did not notably affect the lag time. The morphologies of fibrils, which were monitored by total internal reflection fluorescence microscopy, atomic force microscopy, and transmission electron microscopy, revealed that the length of Aβ-(1–40) fibrils became shorter and the amount of amorphous aggregates became larger as liposomes increased in size. These results suggest that the curvature of membranes coupled with an increase in water-accessible hydrophobic regions is important for binding and concentrating Aβ monomers, leading to amyloid nucleation. Furthermore, amyloid fibrillation on membranes may compete with non-productive binding to produce amorphous aggregates.

71274

Small Liposomes Accelerate the Fibrillation of Amyloid β (1–40)

American Society for Biochemistry and Molecular Biology

英語

2015-01

Journal of Biological Chemistry

290

2

815

826

https://doi.org/10.1074/jbc.M114.592527

https://hdl.handle.net/11094/71274