Featured Research

from universities, journals, and other organizations

New Parkinson's disease chemical messenger discovered

Date:
March 27, 2014
Source:
University of Dundee
Summary:
A new chemical messenger that is critical in protecting the brain against Parkinson's disease has been identified by scientists. The research team had previously discovered that mutations in two genes -- called PINK1 and Parkin -- lead to Parkinson's. Now they have made a completely unexpected discovery about the way the two genes interact, which they say could open up exciting new avenues for research around Parkinson's and offer new drug targets.

A new chemical messenger that is critical in protecting the brain against Parkinson's disease has been identified by scientists at the Medical Research Council (MRC) Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee.

The research team led by Dr Miratul Muqit had previously discovered that mutations in two genes -- called PINK1 and Parkin -- lead to Parkinson's.

Now they have made a completely unexpected discovery about the way the two genes interact, which they say could open up exciting new avenues for research around Parkinson's and offer new drug targets. The results of their research are published in Biochemical Journal.

"Understanding the fundamental mechanisms of how brain cells die in Parkinson's is likely to uncover new insights into how to treat this progressive disorder," said Dr Muqit, a Wellcome Trust Senior Clinical Fellow and Consultant Neurologist at the MRC Protein Phosphorylation and Ubiquitylation Unit at Dundee.

"Our previous research had mapped out a key pathway involving the PINK1 and Parkin genes that when disrupted by mutations led to Parkinson's disease. However, we still did not understand the molecular details of how this pathway was controlled.

"Our new work suggests a chemical messenger called phospho-ubiquitin, is protective and can't be made in Parkinson's patients with genetic mutations in PINK1. This leaves their brain cells vulnerable to stress and likely to trigger cell death."

Dr Muqit's team had already found that the PINK1 and Parkin genes encode for important enzymes that protect brain cells. In patients with mutations in PINK1 and Parkin the protective effects of these enzymes is lost and brain cells controlling movement are damaged, resulting in Parkinson's.

Previous work revealed that the PINK1 enzyme protects survival of brain cells by switching on Parkin, but how this occurred was unknown and in itself formed a major area of research.

Now they have worked out how the two genes interact. They have uncovered that the role of the PINK1 enzyme is to generate a novel chemical messenger molecule termed `phospho-ubiquitin'.

Their research shows that phospho-ubiquitin then functions to directly switch on the Parkin enzyme.

"The data suggests that phospho-ubiquitin molecules will play a critical role in protecting brain cells and thus patients from developing Parkinson's disease," said Dr Muqit.

"This research opens up new exciting avenues for future research that include studying whether low levels of the phospho-ubiquitin molecule are a common feature and cause of Parkinson's. The new data also suggests that it might be possible to develop drugs to better treat Parkinson's that can switch on the Parkin enzyme by mimicking phospho-ubiquitin."

Professor Dario Alessi, Director of the MRC unit at Dundee and a co-author on the study, added, "Now that we have identified this new chemical messenger, it will be important to determine its role in Parkinson's patients. Whilst more work is needed, our findings suggest that designing drugs that mirror phospho-ubiquitin could represent an exciting approach to develop an urgently needed novel therapy for Parkinson's patients."

Claire Bale, Research Communications Manager at Parkinson's UK, said, "This exciting research has revealed the 'missing link' between two key proteins known to be important in Parkinson's.

"We have known for some time that the PINK1 and Parkin proteins work together to protect the precious brain cells that are lost in Parkinson's, but we weren't sure how.

"This new study is the first to reveal that PINK1 produces a vital chemical messenger called 'phospho-ubiquitin' which is essential for switching on Parkin's protective effects.

"This discovery provides a completely new avenue for developing treatments that can tackle the root causes of brain cell death and could ultimately take us closer to a cure for Parkinson's."

David Carling, Deputy Chair of the Biochemical Journal Editorial Board, said, "The study by Dr Muqit and colleagues provides a breakthrough in understanding how two proteins, previously shown to play important roles in Parkinson's disease, interact with one another. This new work opens up a number of avenues for further research and will help in identifying drugs aimed at combatting this devastating disease. We are pleased to be able to publish this exciting study in the Biochemical Journal."


Story Source:

The above story is based on materials provided by University of Dundee. The original article was written by Roddy Isles. Note: Materials may be edited for content and length.


Journal Reference:

  1. Agne Kazlauskaite, Chandana Kondapalli, Robert Gourlay, David Campbell, Maria Stella Ritorto, Kay Hofmann, Dario Alessi, Axel Knebel, Matthias Trost, Miratul Muqit. Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Serine65. Biochemical Journal, 2014; DOI: 10.1042/BJ20140334

Cite This Page:

University of Dundee. "New Parkinson's disease chemical messenger discovered." ScienceDaily. ScienceDaily, 27 March 2014. <www.sciencedaily.com/releases/2014/03/140327222452.htm>.
University of Dundee. (2014, March 27). New Parkinson's disease chemical messenger discovered. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2014/03/140327222452.htm
University of Dundee. "New Parkinson's disease chemical messenger discovered." ScienceDaily. www.sciencedaily.com/releases/2014/03/140327222452.htm (accessed September 17, 2014).

Share This



More Health & Medicine News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Obama Orders Military Response to Ebola

Obama Orders Military Response to Ebola

AP (Sep. 16, 2014) Calling the Ebola outbreak in West Africa a potential threat to global security, President Barack Obama is ordering 3,000 U.S. military personnel to the stricken region amid worries that the outbreak is spiraling out of control. (Sept. 16) Video provided by AP
Powered by NewsLook.com
UN: 20,000 Could Be Infected With Ebola by Year End

UN: 20,000 Could Be Infected With Ebola by Year End

AFP (Sep. 16, 2014) Nearly $1.0 billion dollars is needed to fight the Ebola outbreak raging in west Africa, the United Nations say, warning that 20,000 could be infected by year end. Duration: 00:40 Video provided by AFP
Powered by NewsLook.com
Obama: Ebola Outbreak Threat to Global Security

Obama: Ebola Outbreak Threat to Global Security

AP (Sep. 16, 2014) President Obama is ordering U.S. military personnel to West Africa to deal with the Ebola outbreak, which is he calls a potential threat to global security. (Sept. 16) Video provided by AP
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