Featured Research

from universities, journals, and other organizations

'Molecular switch' discovered in Parkinson's protein

Date:
January 23, 2014
Source:
Kassel, Universität
Summary:
In one variant of Parkinson’s disease, the enzyme LRRK2, plays a central role. Scientists have now discovered a mechanism that controls the activity of LRRK2. This opens up new approaches for the development of drugs to counter the disease, which until now is incurable.

In one variant of Parkinson's disease, the enzyme LRRK2 plays a central role. Scientists at the University of Kassel have now discovered a mechanism that controls the activity of LRRK2. This opens up new approaches for the development of drugs to counter the disease, which until now is incurable.

Following Alzheimer's, Parkinson's disease is the most frequently occurring neuro-degenerative illness. It is estimated that approximately 7 million people suffer from the disease worldwide. A portion of these cases have a hereditary basis and are caused by mutations in specific genes. These so-called familial Parkinson's variants occur with varying degrees of frequency in different ethnic groups; certain mutations are particularly widespread in Italy and Spain, for example. Mutations of a protein called LRRK2 are seen as the most frequent cause of inherited Parkinson's disease.

A research group with scientists from Kassel University has now discovered the "molecular switch" that controls the activity of this protein. "Our results can show ways to develop new drugs to regulate the activity of this protein and thus provide new approaches for the treatment of inherited Parkinson's disease," explains Prof. Dr. Friedrich W. Herberg, head of the Department of Biochemistry at Kassel University. "It may also be possible to derive approaches for the treatment of other variants of Parkinson's from these results."

The protein LRRK2 is also called "dardarin" from the Basque term "dardara" which means "to tremble." In human cells, the protein has a mediating function as it delivers phosphates to other proteins. Dardarin has a special and until now not fully clarified role in certain cells of the midbrain which produce the neurotransmitter dopamine. These cells in the midbrain die in persons suffering from Parkinson's. The resulting lack of dopamine leads to the well-known Parkinson's symptoms such as muscle tremors, depression or the loss of the sense of smell.

The Kassel researchers have investigated individual areas of the enzyme dardarin very closely. "Proteins are made up of smaller building blocks -- amino acids. We were able to determine that in dardarin mutations, which are taken to be responsible for inherited Parkinson's, the phosphate supply is disturbed in an area around the amino acid 1441," explains Dipl. Biol. Kathrin Muda, one of the authors of a study that has now appeared in the journal "Proceedings of the National Academy of Science." "In particular, we found that an additional protein called a 14-3-3 protein can bind in the area 1441 and thus have an effect on the activity of dardarin. In the mutated variants the binding at the dardarin enzyme is disturbed and the activity of dardarin is no longer correctly regulated." How this then results in the dying off of cells in the middle brain is not yet known. "If a way is found to substitute the binding with 14-3-3 through another mechanism that takes the place of the mutated dardarin variants, then we will have taken a big step in the development of anti-Parkinson's drugs," says Muda.

In cooperation with scientists from Tübingen University, from the Helmholtz Center Munich and the German Cancer Research Center Heidelberg, the Kassel researchers make use of so-called mass spectrometry, a process for the weighing of atoms and molecules. Through a comparison of the weight of normal and mutated LRRK2 protein particles, it was possible to draw conclusions about the phosphate supply process in the cells.


Story Source:

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


Journal Reference:

  1. K. Muda, D. Bertinetti, F. Gesellchen, J. S. Hermann, F. von Zweydorf, A. Geerlof, A. Jacob, M. Ueffing, C. J. Gloeckner, F. W. Herberg. Parkinson-related LRRK2 mutation R1441C/G/H impairs PKA phosphorylation of LRRK2 and disrupts its interaction with 14-3-3. Proceedings of the National Academy of Sciences, 2013; 111 (1): E34 DOI: 10.1073/pnas.1312701111

Cite This Page:

Kassel, Universität. "'Molecular switch' discovered in Parkinson's protein." ScienceDaily. ScienceDaily, 23 January 2014. <www.sciencedaily.com/releases/2014/01/140123075631.htm>.
Kassel, Universität. (2014, January 23). 'Molecular switch' discovered in Parkinson's protein. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2014/01/140123075631.htm
Kassel, Universität. "'Molecular switch' discovered in Parkinson's protein." ScienceDaily. www.sciencedaily.com/releases/2014/01/140123075631.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) — Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
Powered by NewsLook.com
Why Do People Believe We Only Use 10 Percent Of Our Brains?

Why Do People Believe We Only Use 10 Percent Of Our Brains?

Newsy (July 22, 2014) — The new sci-fi thriller "Lucy" is making people question whether we really use all our brainpower. But, as scientists have insisted for years, we do. Video provided by Newsy
Powered by NewsLook.com
Scientists Find New Way To Make Human Platelets

Scientists Find New Way To Make Human Platelets

Newsy (July 22, 2014) — Boston scientists have discovered a new way to create fully functioning human platelets using a bioreactor and human stem cells. Video provided by Newsy
Powered by NewsLook.com
Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) — New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
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