Featured Research

from universities, journals, and other organizations

Neurodegenerative diseases: New findings on protein misfolding

Date:
September 18, 2012
Source:
Helmholtz Association of German Research Centres
Summary:
Misfolded proteins can cause various neurodegenerative diseases such as spinocerebellar ataxias or Huntington's disease, which are characterized by a progressive loss of neurons in the brain. Researchers have now identified 21 proteins that specifically bind to the protein ataxin-1. Twelve of these proteins enhance the misfolding of ataxin-1 and thus promote the formation of harmful protein aggregate structures.

Misfolded proteins can cause various neurodegenerative diseases such as spinocerebellar ataxias (SCAs) or Huntington's disease, which are characterized by a progressive loss of neurons in the brain. Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, together with their colleagues of the Université Paris Diderot, Paris, France, have now identified 21 proteins that specifically bind to a protein called ataxin-1. Twelve of these proteins enhance the misfolding of ataxin-1 and thus promote the formation of harmful protein aggregate structures, whereas nine of them prevent the misfolding.

Proteins only function properly when the chains of amino acids, from which they are built, fold correctly. Misfolded proteins can be toxic for the cells and assemble into insoluble aggregates together with other proteins. Ataxin-1, the protein that the researchers have now investigated, is very prone to misfolding due to inherited gene defects that cause neurodegenerative diseases. The reason for this is that the amino acid glutamine is repeated in the amino acid chain of ataxin-1 very often -- the more glutamine, the more toxic the protein. Approximately 40 repeats of glutamine are considered to be toxic for the cells.

Now, Dr. Spyros Petrakis, Dr. Miguel Andrade, Professor Erich Wanker and colleagues have identified 21 proteins that mainly interact with ataxin-1 and influence its folding or misfolding. Twelve of these proteins enhance the toxicity of ataxin-1 for the nerve cells, whereas nine of the identified proteins reduce its toxicity.

Furthermore, the researchers detected a common feature in the structure of those proteins that enhances toxicity and aggregation. It is a special structure scientists call "coiled-coil-domain" because it resembles a double twisted spiral or helix. Apparently this structure promotes aggregation, because proteins that interact with ataxin-1 and have this domain enhance the toxic effect of mutated ataxin-1. As the researchers said, this structure could be a potential target for therapy: "A careful analysis of the molecular details could help to discover drugs that suppress toxic processes."


Story Source:

The above story is based on materials provided by Helmholtz Association of German Research Centres. Note: Materials may be edited for content and length.


Journal Reference:

  1. Spyros Petrakis, Tamás Raskó, Jenny Russ, Ralf P. Friedrich, Martin Stroedicke, Sean-Patrick Riechers, Katja Muehlenberg, Angeli Möller, Anita Reinhardt, Arunachalam Vinayagam, Martin H. Schaefer, Michael Boutros, Hervé Tricoire, Miguel A. Andrade-Navarro, Erich E. Wanker. Identification of Human Proteins That Modify Misfolding and Proteotoxicity of Pathogenic Ataxin-1. PLoS Genetics, 2012; 8 (8): e1002897 DOI: 10.1371/journal.pgen.1002897

Cite This Page:

Helmholtz Association of German Research Centres. "Neurodegenerative diseases: New findings on protein misfolding." ScienceDaily. ScienceDaily, 18 September 2012. <www.sciencedaily.com/releases/2012/09/120918113053.htm>.
Helmholtz Association of German Research Centres. (2012, September 18). Neurodegenerative diseases: New findings on protein misfolding. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2012/09/120918113053.htm
Helmholtz Association of German Research Centres. "Neurodegenerative diseases: New findings on protein misfolding." ScienceDaily. www.sciencedaily.com/releases/2012/09/120918113053.htm (accessed July 31, 2014).

Share This




More Mind & Brain News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dieting At A Young Age Might Lead To Harmful Health Habits

Dieting At A Young Age Might Lead To Harmful Health Habits

Newsy (July 30, 2014) — Researchers say women who diet at a young age are at greater risk of developing harmful health habits, including eating disorders and alcohol abuse. Video provided by Newsy
Powered by NewsLook.com
It's Not Just Facebook: OKCupid Experiments With Users Too

It's Not Just Facebook: OKCupid Experiments With Users Too

Newsy (July 29, 2014) — If you've been looking for love online, there's a chance somebody has been looking at how you're looking. Video provided by Newsy
Powered by NewsLook.com
How Your Face Can Leave A Good Or Bad First Impression

How Your Face Can Leave A Good Or Bad First Impression

Newsy (July 29, 2014) — Researchers have found certain facial features can make us seem more attractive or trustworthy. Video provided by Newsy
Powered by NewsLook.com
Losing Sleep Leaves You Vulnerable To 'False Memories'

Losing Sleep Leaves You Vulnerable To 'False Memories'

Newsy (July 27, 2014) — A new study shows sleep deprivation can make it harder for people to remember specific details of an event. 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:
from the past week

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