Featured Research

from universities, journals, and other organizations

New Route To Parkinson's Found In Cells' 'Garbage Disposal' System

Date:
December 31, 2004
Source:
Cell Press
Summary:
Researchers have known that mutations in a key gene called parkin are a major cause of Parkinson's disease (PD). Now they have discovered a new mechanism by which the parkin gene can be compromised, a finding that they say could lead to new drugs for the disorder.

Researchers have known that mutations in a key gene called parkin are a major cause of Parkinson's disease (PD). Now they have discovered a new mechanism by which the parkin gene can be compromised, a finding that they say could lead to new drugs for the disorder.

Andrea Lozano, Senior Scientist at the Toronto Western Research Institute, of University Health Network and Professor of Surgery at the University of Toronto and colleagues found that the protein produced by a gene called BAG5 inhibits parkin activity and the action of another protein, called Hsp70, a "chaperone" that works with parkin. They found in studies with rats that BAG5 enhances the death of the dopaminergic neurons targeted by Parkinson's and that inhibiting the gene reduces such death.

Parkin is part of the cell's "garbage disposal" system that rids the cell of unwanted proteins by degrading them. Mutations of parkin eliminate its ability to chemically "tag" such proteins to designate them for destruction in the cell's proteasome--a process called ubiquitinylation. Loss of such ability causes such protein garbage to aggregate into lethal clumps in neurons--a hallmark of many neurodegenerative diseases. In the brain, the parkin protein works with Hsp70, which helps correct the folding of misfolded proteins.

BAG5 is one of a family of BAG proteins known to interact with other proteins to aid a variety of cell processes. The structure of BAG5 led Lozano and colleagues to explore whether it might play a role in the proteasome, along with parkin and Hsp70.

Their experiments revealed that BAG5 was activated when dopaminergic neurons were injured, suggesting a role in neurodegeneration. Experiments also revealed that BAG5 inhibits Hsp70 and interacts directly with parkin, inhibiting its activity. This inhibition, they found, enhances the formation of protein aggregates, and this formation was inhibited when the researchers shut down the activity of BAG5. In other test tube studies, the researchers also found that BAG5 inhibited parkin's ability to protect cells against proteasome dysfunction and cell death.

In experiments with rats, the researchers found that BAG5 enhanced the degeneration of dopaminergic neurons and that inhibiting BAG5 increased neuronal survival.

"Based on our findings, we propose a novel mechanism for neurodegeneration in which BAG5 interacts with both parkin and Hsp70, resulting in decreased parkin and Hsp70 function, two outcomes that are deleterious to cell survival," concluded the researchers. "Given the role of BAG5 in modulating ubiquitinylation, protein aggregation, and cell death, it may serve as a useful therapeutic target for neurodegenerative diseases such as PD."

###

The other members of the research team include Suneil K. Kalia, Sang Lee, and Li Liu, of the Toronto Western Research Institute of the University of Toronto; Patrice D. Smith, Stephen J. Crocker, and David S. Park, of the Neuroscience Research Institute of the University of Ottawa; Thorhildur E. Thorarinsdottir and Edward A. Fon, of the Centre for Neuronal Survival of McGill University; and John R. Glover, of the Department of Biochemistry of the University of Toronto. This work was supported by the Canadian Institutes of Health Research (CIHR) (S.K.K., J.R.G., E.A.F., D.S.P., A.M.L.); Michael J. Fox Foundation (T.E.T.); and Parkinson's Society of Canada (D.S.P.).

Suneil K. Kalia, Sang Lee, Patrice D. Smith, Li Liu, Stephen J. Crocker, Thorhildur E. Thorarinsdottir, John R. Glover, Edward A. Fon, David S. Park, and Andres M. Lozano: "BAG5 Inhibits Parkin and Enhances Dopaminergic Neuron Degeneration"

The context and implications of this work are discussed in a Preview by Kenny K.K. Chung and Ted M. Dawson of the Johns Hopkins University School of Medicine.

Publishing in Neuron, Volume 44, Number 6, December 16, 2004, pages 931–945. http://www.neuron.org/.


Story Source:

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


Cite This Page:

Cell Press. "New Route To Parkinson's Found In Cells' 'Garbage Disposal' System." ScienceDaily. ScienceDaily, 31 December 2004. <www.sciencedaily.com/releases/2004/12/041219195508.htm>.
Cell Press. (2004, December 31). New Route To Parkinson's Found In Cells' 'Garbage Disposal' System. ScienceDaily. Retrieved September 14, 2014 from www.sciencedaily.com/releases/2004/12/041219195508.htm
Cell Press. "New Route To Parkinson's Found In Cells' 'Garbage Disposal' System." ScienceDaily. www.sciencedaily.com/releases/2004/12/041219195508.htm (accessed September 14, 2014).

Share This



More Health & Medicine News

Sunday, September 14, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Respiratory Virus Spreads To Northeast, Now In 21 States

Respiratory Virus Spreads To Northeast, Now In 21 States

Newsy (Sep. 14, 2014) The respiratory virus Enterovirus D68, which targets children, has spread from the Midwest to 21 states. Video provided by Newsy
Powered by NewsLook.com
Shocker: Journalists Are Utterly Addicted To Coffee

Shocker: Journalists Are Utterly Addicted To Coffee

Newsy (Sep. 13, 2014) A U.K. survey found that journalists consumed the most amount of coffee, but that's only the tip of the coffee-related statistics iceberg. Video provided by Newsy
Powered by NewsLook.com
Contagious Respiratory Illness Continues to Spread Across U.S.

Contagious Respiratory Illness Continues to Spread Across U.S.

Reuters - US Online Video (Sep. 12, 2014) Hundreds of children in several states have been stricken by a serious respiratory illness that is spreading across the U.S. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Batters Sierra Leone Economy Too

Ebola Batters Sierra Leone Economy Too

Reuters - Business Video Online (Sep. 12, 2014) The World Health Organisation warns that local health workers in West Africa can't keep up with Ebola - and among those countries hardest hit by the outbreak, the economic damage is coming into focus, too. As David Pollard reports, Sierra Leone admits that growth in one of the poorest economies in the region is taking a beating. 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:
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