1. Most Discussed
  2. Gainers & Losers
PBT 4.6¢

Cu2+ and AD oligomers - published by Prana scientists

  1. interestingtome

    1,847 Posts.
    1
    Small Angle x-ray Scattering

    Tim M Ryan, Nigel Kirby, Chi L. L. Pham, Blaine R Roberts, Haydyn Mertens, Kevin Jeffrey Barnham, Roberto Cappai, Colin Masters and Cyril C. Curtain

    Metallomics, 2015, Accepted Manuscript

    DOI: 10.1039/C4MT00323C​
    Received 04 Dec 2014, Accepted 09 Feb 2015
    First published online 09 Feb 2015

    Abstract

    Research into causes of Alzheimer’s disease and its treatment has produced tantalising array of hypotheses about the role of transition metal dyshomeostasis, many of them on the interaction of these metals with the neurotoxic amyloid-β peptide (Aβ). Here, we have used small angle X-ray scattering (SAXS) to study the effect of the molar ratio, Cu2+/ Aβ, on the early three-dimensional structures of the Aβ1-40 and Cu2+/ Aβ1-42 peptides in solution. We found that at molar ratios of 0.5 copper to peptide Aβ1-40 aggregated, while Aβ1-42 adopted a relatively monodisperse cylindrical shape, and at a ratio of 1.5 copper to peptide Aβ1-40 adopted a monodisperse cylindrical shape, while Aβ1-42 adopted the shape of an ellipsoid of rotation. We also found, via in-line rapid mixing SAXS analysis, that both peptides in the absence of copper were monodisperse at very short timeframes (<2 sec). Kratky plots of these scattering profiles indicated that immediately after mixing both were intrinsically disordered. Ensemble optimisation modelling reflected this, indicating a wide range of structural conformers. These data reflect the ensembles from which the Cu2+-promoted oligomers were derived. Our results are discussed in the light of other studies that have shown that the Cu2+/ Aβ has a marked effect on fibril and oligomer formation by this peptide, with a higher ratio favouring the formation of cytotoxic non-amyloid oligomers. Our results are relatively consistent with previous two-dimensional studies of the conformations of these Cu2+- induced entities, made on a much longer time-scale than SAXS, by transmission electron microscopy and atomic force microscopy, which showed that a range of oligomeric species are formed. We propose that SAXS carried out on a modern synchrotron beamline enables studies on initial events in disordered protein folding on physiologically-relevant time-scales, and will likely provide great insight into the initiating processes of the Aβ misfolding, oligomerisation and amyloid formation.

DISCLAIMER:
Before making any financial decisions based on what you read, always consult an advisor or expert.

The HotCopper website is operated by Report Card Pty Ltd. Any information posted on the website has been prepared without taking into account your objectives, financial situation or needs and as such, you should before acting on the information or advice, consider the appropriateness of the information or advice in relation to your objectives, financial situation or needs. Please be aware that any information posted on this site should not be considered to be financial product advice.

From time to time comments aimed at manipulating other investors may appear on these forums. Posters may post overly optimistic or pessimistic comments on particular stocks, in an attempt to influence other investors. It is not possible for management to moderate all posts so some misleading and inaccurate posts may still appear on these forums. If you do have serious concerns with a post or posts you should report a Terms of Use Violation (TOU) on the link above. Unless specifically stated persons posting on this site are NOT investment advisors and do NOT hold the necessary licence, or have any formal training, to give investment advice.

Top

Thank you for visiting HotCopper

We have detected that you are running ad blocking software.


HotCopper relies on revenue generated from advertisers. Kindly disable your ad blocking software to return to the HotCopper website.

I understand, I have disabled my ad blocker. Let me in!

Need help? Click here for support.