Featured Research

from universities, journals, and other organizations

Mutation in a protein-sorting gene is linked with Parkinson's disease

Date:
July 14, 2011
Source:
Cell Press
Summary:
Parkinson disease (PD) is a devastating incurable disease in which degeneration of dopamine neurons in the brainstem leads to tremors and problems with movement and coordination. An increasing proportion of patients appear to be genetically predisposed to disease. Now, two independent research groups have identified a mutation associated with an inherited form of PD. The papers provide new insight into the pathogenesis of late-onset PD and present compelling evidence that implicates a novel protein-recycling pathway in neurodegeneration.

Parkinson disease (PD) is a devastating incurable disease in which degeneration of dopamine neurons in the brainstem leads to tremors and problems with movement and coordination. An increasing proportion of patients appear to be genetically predisposed to disease. Now, two independent research groups have identified a mutation associated with an inherited form of PD.

Related Articles


The papers, published by Cell Press in the July 9 issue of The American Journal of Human Genetics, provide new insight into the pathogenesis of late-onset PD and present compelling evidence that implicates a novel protein-recycling pathway in neurodegeneration.

"Previous studies of familial parkinsonism have identified pathogenic mutations in several genes, providing mechanistic insight and novel targets for therapeutic intervention," say the lead authors of one of the studies, Dr. Carles Vilariño-Güell and Dr. Matthew J. Farrer from the University of British Columbia. "In our study, we identified a pathogenic mutation associated with PD in a Swiss family where multiple individuals presented with disease. Confirmation of the discovery was an international effort embraced by neurologists in Canada, Israel, Norway, Switzerland, Taiwan, Tunisia, and the United States."

A second independent study, led by Dr. Tim M. Strom from the Institute of Human Genetics in Neuherberg, Germany and Dr. Alexander Zimprich from the Medical University of Vienna, used the same sophisticated sequencing techniques to look for causal mutations in a family from Austria with multiple incidences of late-onset PD.

Both groups discovered the same mutation in the vacuolar protein-sorting-associated protein 35 (VPS35) gene in affected family members. The VPS35 protein is part of a complex called the "retromer" that mediates the intracellular transport and sorting of membrane-associated cell-surface proteins that are going to be recycled or destroyed. "A single variant in the VPS35 gene was found in all affected family members investigated, was absent in general population samples, and was detected in two additional PD families," say Dr. Strom and Dr. Zimprich.

Taken together, the findings suggest that the VPS35 mutation is the genetic determinant of the late-onset PD examined in the studies and that perturbation of retromer-mediated protein sorting is linked with neurodegeneration. Interestingly, recent studies have suggested that retromer sorting defects are also associated with Alzheimer disease.

"Screening of VPS35 and its interacting partners, not only in PD patients but in other movement and cognitive disorders, is warranted to fully understand the role of the retromer in disease development. However, it is unclear how mutant VPS35 impairs retromer function or the transport of specific cargos or why dopaminergic neurons are selectively vulnerable," concludes Dr. Farrer's team. "Model systems based on VPS35 mutations can now focus on these issues and will facilitate the development of novel therapeutics."


Story Source:

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


Journal References:

  1. Carles Vilariño-Güell, Christian Wider, Owen A. Ross, Justus C. Dachsel, Jennifer M. Kachergus, Sarah J. Lincoln, Alexandra I. Soto-Ortolaza, Stephanie A. Cobb, Greggory J. Wilhoite, Justin A. Bacon, Bahareh Behrouz, Heather L. Melrose, Emna Hentati, Andreas Puschmann, Daniel M. Evans, Elizabeth Conibear, Wyeth W. Wasserman, Jan O. Aasly, Pierre R. Burkhard, Ruth Djaldetti, Joseph Ghika, Faycal Hentati, Anna Krygowska-Wajs, Tim Lynch, Eldad Melamed, Alex Rajput, Ali H. Rajput, Alessandra Solida, Ruey-Meei Wu, Ryan J. Uitti, Zbigniew K. Wszolek, François Vingerhoets, Matthew J. Farrer. VPS35 Mutations in Parkinson Disease. American Journal of Human Genetics, 2011; 89 (1): 162-167 DOI: 10.1016/j.ajhg.2011.06.001
  2. Alexander Zimprich, Anna Benet-Pagès, Walter Struhal, Elisabeth Graf, Sebastian H. Eck, Marc N. Offman, Dietrich Haubenberger, Sabine Spielberger, Eva C. Schulte, Peter Lichtner, Shaila C. Rossle, Norman Klopp, Elisabeth Wolf, Klaus Seppi, Walter Pirker, Stefan Presslauer, Brit Mollenhauer, Regina Katzenschlager, Thomas Foki, Christoph Hotzy, Eva Reinthaler, Ashot Harutyunyan, Robert Kralovics, Annette Peters, Fritz Zimprich, Thomas Brücke, Werner Poewe, Eduard Auff, Claudia Trenkwalder, Burkhard Rost, Gerhard Ransmayr, Juliane Winkelmann, Thomas Meitinger, Tim M. Strom. A Mutation in VPS35, Encoding a Subunit of the Retromer Complex, Causes Late-Onset Parkinson Disease. American Journal of Human Genetics, 2011; 89 (1): 168-175 DOI: 10.1016/j.ajhg.2011.06.008

Cite This Page:

Cell Press. "Mutation in a protein-sorting gene is linked with Parkinson's disease." ScienceDaily. ScienceDaily, 14 July 2011. <www.sciencedaily.com/releases/2011/07/110714132116.htm>.
Cell Press. (2011, July 14). Mutation in a protein-sorting gene is linked with Parkinson's disease. ScienceDaily. Retrieved January 27, 2015 from www.sciencedaily.com/releases/2011/07/110714132116.htm
Cell Press. "Mutation in a protein-sorting gene is linked with Parkinson's disease." ScienceDaily. www.sciencedaily.com/releases/2011/07/110714132116.htm (accessed January 27, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, January 27, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Mistakes Should Serve a Lesson Says WHO

Ebola Mistakes Should Serve a Lesson Says WHO

AFP (Jan. 25, 2015) — The World Health Organization&apos;s chief on Sunday admitted the UN agency had been caught napping on Ebola, saying it should serve a lesson to avoid similar mistakes in future. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Disneyland Measles Outbreak Spreads To 5 States

Disneyland Measles Outbreak Spreads To 5 States

Newsy (Jan. 24, 2015) — Much of the Disneyland measles outbreak is being blamed on the anti-vaccination movement. The CDC encourages just about everyone get immunized. Video provided by Newsy
Powered by NewsLook.com
Growing Measles Outbreak Worries Calif. Parents

Growing Measles Outbreak Worries Calif. Parents

AP (Jan. 23, 2015) — Public health officials are rushing to contain a measles outbreak that has sickened 70 people across 6 states and Mexico. The AP&apos;s Raquel Maria Dillon has more. (Jan. 23) Video provided by AP
Powered by NewsLook.com
Smart Wristband to Shock Away Bad Habits

Smart Wristband to Shock Away Bad Habits

Reuters - Innovations Video Online (Jan. 23, 2015) — A Boston start-up is developing a wristband they say will help users break bad habits by jolting them with an electric shock. Ben Gruber reports. Video provided by Reuters
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:

More Coverage


New Link Between Parkinson’s Disease and Cellular Sorting

July 19, 2011 — Scientists have identified a mutation associated with a inherited form of late-onset Parkinson's disease. The mutation occurs in a gene that plays a role in intracellular protein ... read more

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