Diverse Structural Conversion and Aggregation Pathways of Alzheimerʼs Amyloid‑β (1–40)

Complex amyloid aggregation of amyloid-β (1–40) (Aβ1–40) in terms of monomer structures has not been fully understood. Herein, we report the microscopic mechanism and pathways of Aβ1–40 aggregation with macroscopic viewpoints through tuning its initial structure and solubility. Partial helical struc...

Full description

Saved in:
Bibliographic Details
Published in:ACS nano 2019-08, Vol.13 (8), p.8766-8783
Main Authors: Lin, Yuxi, Sahoo, Bikash R, Ozawa, Daisaku, Kinoshita, Misaki, Kang, Juhye, Lim, Mi Hee, Okumura, Masaki, Huh, Yang Hoon, Moon, Eunyoung, Jang, Jae Hyuck, Lee, Hyun-Ju, Ryu, Ka-Young, Ham, Sihyun, Won, Hyung-Sik, Ryu, Kyoung-Seok, Sugiki, Toshihiko, Bang, Jeong Kyu, Hoe, Hyang-Sook, Fujiwara, Toshimichi, Ramamoorthy, Ayyalusamy, Lee, Young-Ho
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Complex amyloid aggregation of amyloid-β (1–40) (Aβ1–40) in terms of monomer structures has not been fully understood. Herein, we report the microscopic mechanism and pathways of Aβ1–40 aggregation with macroscopic viewpoints through tuning its initial structure and solubility. Partial helical structures of Aβ1–40 induced by low solvent polarity accelerated cytotoxic Aβ1–40 amyloid fibrillation, while predominantly helical folds did not aggregate. Changes in the solvent polarity caused a rapid formation of β-structure-rich protofibrils or oligomers via aggregation-prone helical structures. Modulation of the pH and salt concentration transformed oligomers to protofibrils, which proceeded to amyloid formation. We reveal diverse molecular mechanisms underlying Aβ1–40 aggregation with conceptual energy diagrams and propose that aggregation-prone partial helical structures are key to inducing amyloidogenesis. We demonstrate that context-dependent protein aggregation is comprehensively understood using the macroscopic phase diagram, which provides general insights into differentiation of amyloid formation and phase separation from unfolded and folded structures.
ISSN:1936-0851
1936-086X
DOI:10.1021/acsnano.9b01578