[NMR paper] Structural Insight into an Alzheimer's Brain-Derived Spherical Assembly of Amyloid ? by Solid-state NMR.

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Structural Insight into an Alzheimer's Brain-Derived Spherical Assembly of Amyloid ? by Solid-state NMR.

Related Articles Structural Insight into an Alzheimer's Brain-Derived Spherical Assembly of Amyloid ? by Solid-state NMR.

J Am Chem Soc. 2015 May 4;

Authors: Parthasarathy S, Inoue M, Xiao Y, Matsumura Y, Nabeshima YI, Hoshi M, Ishii Y

Abstract
Accumulating evidence suggests that various neurodegenerative diseases, including Alzheimer's 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-? (A?). Electron mi-croscopy and immunological analyses using ASPD-specific 'conformational' antibodies established synthetic ASPD for the 42-residue A?(1-42) as an excellent struc-tural/morphological analog of native ASPD extracted from AD patients, the level of which correlates with the severity of AD. 13C solid-state NMR (SSNMR) analyses of approximately 20 residues and inter-strand distances demonstrated that the synthetic ASPD is made of a ho-mogeneous single conformer containing parallel ?-sheets. These results provide profound insight into the native ASPD indicating that A? is likely to self-assemble into the toxic intermediate with ?-sheet structures in AD brains. This approach can be applied to various interme-diates relevant to amyloid diseases.


PMID: 25938164 [PubMed - as supplied by publisher]



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