Diverse Structural Conversion and Aggregation Pathways of Alzheimer's Amyloid-beta (1-40)

Cited 0 time in webofscience Cited 0 time in scopus
  • Hit : 16
  • Download : 0
Complex amyloid aggregation of amyloid-beta (1-40) (A beta(1-40)) in terms of monomer structures has not been fully understood. Herein, we report the microscopic mechanism and pathways of A beta(1-40) aggregation with macroscopic viewpoints through tuning its initial structure and solubility. Partial helical structures of A beta(1-40) induced by low solvent polarity accelerated cytotoxic A beta(1-40) amyloid fibrillation, while predominantly helical folds did not aggregate. Changes in the solvent polarity caused a rapid formation of beta-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 A beta(1-40) 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.
Publisher
AMER CHEMICAL SOC
Issue Date
2019-08
Language
English
Article Type
Article
Citation

ACS NANO, v.13, no.8, pp.8766 - 8783

ISSN
1936-0851
DOI
10.1021/acsnano.9b01578
URI
http://hdl.handle.net/10203/267636
Appears in Collection
CH-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0