Featured Research

from universities, journals, and other organizations

Alzheimer's, Parkinson's and type II diabetes: New way to target shape-shifting proteins

Date:
August 29, 2011
Source:
University of Leeds
Summary:
A molecule which can stop the formation of long protein strands, known as amyloid fibrils, that cause joint pain in kidney dialysis patients has been identified. The discovery could lead to new methods to identify drugs to prevent, treat or halt the progression of other conditions in which amyloid fibrils play a part, including Alzheimer's, Parkinson's and type II diabetes.

A molecule which can stop the formation of long protein strands, known as amyloid fibrils, that cause joint pain in kidney dialysis patients has been identified by researchers at the University of Leeds. The discovery could lead to new methods to identify drugs to prevent, treat or halt the progression of other conditions in which amyloid fibrils play a part, including Alzheimer's, Parkinson's and type II diabetes.

Related Articles


The research, funded by the Biotechnology and Biological Sciences Research Council and the Wellcome Trust, is published August 28 in Nature Chemical Biology.

The team -- from Leeds' Astbury Centre for Structural Molecular Biology and Faculty of Biological Sciences -- found that an antibiotic known as Rifamycin SV was able to prevent the protein β2microglobulin (β2m) from forming into fibrils. β2m is known to accumulate in renal dialysis patients and forms fibrils within the joints, causing extreme pain and arthritis.

By using a specialised analytical technique called ion mobility spectrometry-mass spectrometry (IMS-MS), the researchers were able to see at what stage of the process Rifamycin SV prevented amyloid fibril formation. They believe the technique could enable potential drugs to be identified for the many other proteins which form amyloid fibrils, linked to a wide range of human disorders.

"Traditional drug design for diseases like Alzheimer's is incredibly difficult because the proteins you're trying to target are changing shape and structure all the time," explains University of Leeds Professor of Structural Molecular Biology, Sheena Radford. "It's like trying to consistently pick out one bead of a particular shape from box of potentially millions of similar beads. This new technique allows us to see the shape of the protein as it changes, so we can more easily identify exactly which part we need to target."

In their normal, folded state, proteins are unable to link together to form long fibrillar assemblies, but if they unfold, they expose areas where they can bind to each other. Initially they form small groups of two, three or four proteins, and then these link into long strands, which twist together to form fibrils.

Most analytical techniques can only show the mass of the protein or its make-up in terms of amino acids, neither of which changes as the protein unfolds. Others are unable to look at individual molecules within complex mixtures. However, IMS-MS can measure the mass and shape of a protein, allowing researchers to watch the unfolding process and the aggregation into small groups and then assembly into the fibril and to find which of these species is able to bind a ligand and stop the assembly process.

In the research published August 28, researchers found that Rifamycin SV stopped the formation of protein fibrils by binding to an unfolded protein molecule with a particular shape, enabling for the first time, an unfolded protein of a particular shape to be identified as a target for the design of new inhibitors of fibril assembly.

"We're fortunate to be one of the few universities in the UK able to use IMS-MS to study amyloid fibril formation," says Professor of Biomolecular Mass Spectrometry, Alison Ashcroft, who specialises in this type of analysis. "Although fibrils take years to develop in the body, we are able to 'grow' them in hours in the lab. By using IMS-MS to help us map exactly how they are formed, we can better understand the mechanism by which it happens and -- we hope -- find ways to stop it."


Story Source:

The above story is based on materials provided by University of Leeds. Note: Materials may be edited for content and length.


Journal Reference:

  1. Lucy A Woods, Geoffrey W Platt, Andrew L Hellewell, Eric W Hewitt, Steve W Homans, Alison E Ashcroft, Sheena E Radford. Ligand binding to distinct states diverts aggregation of an amyloid-forming protein. Nature Chemical Biology, 2011; DOI: 10.1038/nchembio.635

Cite This Page:

University of Leeds. "Alzheimer's, Parkinson's and type II diabetes: New way to target shape-shifting proteins." ScienceDaily. ScienceDaily, 29 August 2011. <www.sciencedaily.com/releases/2011/08/110828140938.htm>.
University of Leeds. (2011, August 29). Alzheimer's, Parkinson's and type II diabetes: New way to target shape-shifting proteins. ScienceDaily. Retrieved March 27, 2015 from www.sciencedaily.com/releases/2011/08/110828140938.htm
University of Leeds. "Alzheimer's, Parkinson's and type II diabetes: New way to target shape-shifting proteins." ScienceDaily. www.sciencedaily.com/releases/2011/08/110828140938.htm (accessed March 27, 2015).

Share This


More From ScienceDaily



More Mind & Brain News

Friday, March 27, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

AAA: Distracted Driving a Serious Teen Problem

AAA: Distracted Driving a Serious Teen Problem

AP (Mar. 25, 2015) While distracted driving is not a new problem for teens, new research from the AAA Foundation for Traffic Safety says it&apos;s much more serious than previously thought. (March 25) Video provided by AP
Powered by NewsLook.com
Smartphone Use Changing Our Brain and Thumb Interaction, Say Researchers

Smartphone Use Changing Our Brain and Thumb Interaction, Say Researchers

Reuters - Innovations Video Online (Mar. 25, 2015) European researchers say our smartphone use offers scientists an ideal testing ground for human brain plasticity. Dr Ako Ghosh&apos;s team discovered that the brains and thumbs of smartphone users interact differently from those who use old-fashioned handsets. Jim Drury went to meet him. Video provided by Reuters
Powered by NewsLook.com
Many Don't Know They Have Alzheimer's, But Their Doctors Do

Many Don't Know They Have Alzheimer's, But Their Doctors Do

Newsy (Mar. 24, 2015) According to a new study by the Alzheimer&apos;s Association, more than half of those who have the degenerative brain disease aren&apos;t told by their doctors. Video provided by Newsy
Powered by NewsLook.com
A Quick 45-Minute Nap Can Improve Your Memory

A Quick 45-Minute Nap Can Improve Your Memory

Newsy (Mar. 23, 2015) Researchers found those who napped for 45 minutes to an hour before being tested on information recalled it five times better than those who didn&apos;t. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins