Papers

Peer-reviewed
May, 2015

Structural Insight into an Alzheimer's Brain-Derived Spherical Assembly of Amyloid beta by Solid-State NMR

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
  • Sudhakar Parthasarathy
  • ,
  • Masafumi Inoue
  • ,
  • Yiling Xiao
  • ,
  • Yoshitaka Matsumura
  • ,
  • Yo-ichi Nabeshima
  • ,
  • Minako Hoshi
  • ,
  • Yoshitaka Ishii

Volume
137
Number
20
First page
6480
Last page
6483
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1021/jacs.5b03373
Publisher
AMER CHEMICAL SOC

Accumulating evidence suggests that various neurodegenerative diseases, including Alzheimers disease (AD), are linked to cytotoxic diffusible aggregates of amyloid proteins, which are metastable intermediate species in protein misfolding. This study presents the first site-specific structural study on an intermediate called amylospheroid (ASPD), an AD-derived neurotoxin composed of oligomeric amyloid-beta (A beta). Electron microscopy and immunological analyses using ASPD-specific conformational antibodies established synthetic ASPD for the 42-residue A beta(1-42) as an excellent structural/morphological analogue of native ASPD extracted from AD patients, the level of which correlates with the severity of AD. C-13 solid-state NMR analyses of approximately 20 residues and interstrand distances demonstrated that the synthetic ASPD is made of a homogeneous single conformer containing parallel beta-sheets. These results provide profound insight into the native ASPD, indicating that A beta is likely to self-assemble into the toxic intermediate with beta-sheet structures in AD brains. This approach can be applied to various intermediates relevant to amyloid diseases.

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Link information
DOI
https://doi.org/10.1021/jacs.5b03373
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25938164
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000355383500015&DestApp=WOS_CPL
ID information
  • DOI : 10.1021/jacs.5b03373
  • ISSN : 0002-7863
  • Pubmed ID : 25938164
  • Web of Science ID : WOS:000355383500015

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