Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
Micromedic Technologies

Analysis Reveals Detailed Structural Features of Amyloid Oligomers

By BiotechDaily International staff writers
Posted on 15 Jul 2013
Print article
Image: Molecular structures of amyloid oligomers and amyloid fibers (Photo courtesy of the University of California, Los Angeles).
Image: Molecular structures of amyloid oligomers and amyloid fibers (Photo courtesy of the University of California, Los Angeles).
Advanced analytical analysis of amyloid-beta42 oligomers has yielded insights into the structure of these oligomers that helps to explain the mechanism behind the process of oligomerization and the reasons for their molecular toxicity.

Oligomerization of the 42 amino acid peptide amyloid-beta42 plays a key role in the pathogenesis of Alzheimer disease, but despite great academic and medical interest, the structure of these oligomers has not been well characterized.

In the current study, investigators at the University of California, Los Angeles (USA) employed several advanced analytical techniques to delve the secrets of the oligomeric (globulomeric) form of amyloid-beta42. They reported in the June 28, 2013, issue of the Journal of Biological Chemistry that transmission electron microscopy showed amyloid-beta42 oligomers were globular structures with diameters of about seven to eight nanometers. Circular dichroism revealed primarily beta-structures, while X-ray powder diffraction suggested a highly ordered intrasheet hydrogen-bonding network with heterogeneous intersheet packing. Residue-level mobility analysis on spin labels introduced at 14 different positions showed a structured state but with a disordered state at all labeling sites. Side chain mobility analysis suggested that structural order increased from N- to C-terminal regions. Intermolecular distance measurements at 14 residue positions suggested that C-terminal residues glycine-29 to valine-40 formed a tightly packed core with intermolecular distances in a narrow range of 1.15–1.25 nm.

The authors suggested that the significant structural and organizational differences that distinguished amyloid-beta42 globulomers from the free peptide and amyloid-plaque forms may help to explain the lack of success of experimental anti-Alzheimer's disease drugs that targeted amyloid plaques while ignoring the globulomeric form of the molecule.

Related Links:
University of California, Los Angeles



Print article

Channels

Drug Discovery

view channel
Image: Schematic diagram of dendrimer structure (Photo courtesy of the University of California, Irvine).

Dendrimer-Transported MicroRNA Shown Effective in Treating Mice with Late-Stage Liver Cancer

Cancer researchers have used nanocarriers called dendrimers to transport a specific tumor growth-inhibiting microRNA (miRNA) to the livers of mice with late-stage liver cancer. MicroRNAs are a class... Read more

Business

view channel

Purchase Agreement to Boost Ebola Vaccine Development

A deal to help boost development of a vaccine to protect against Ebolavirus infection was finalized at the recent Davos Conference in Switzerland. Gavi (Geneva, Switzerland), the global alliance for vaccines and immunizations, announced that it would spend five million USD to purchase the Ebola vaccine under development... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.