Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

“Molecular switch” discovered in Parkinson’s protein

23.01.2014
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.

One of the focal points of the working group at Kassel University in their research is investigations of protein kinase A, one of the enzymes that is involved as a mediator in many processes in human cells, as for instance with the phosphate supply of LRRK2. In addition to Herberg and Muda, the Kassel scientists Dr. Daniela Bertinetti and Dipl. Biol. Jennifer Sarah Hermann as well as Dr. Frank Gesellchen from Glasgow were also involved in the research efforts. The Biochemistry Department of Kassel University is part of a consortium for research of human proteins (www.affinomics.org). The study received support from the EU, the Otto Braun Fund and the foundation of the actor Michael J. Fox, a sufferer of Parkinson’s disease, among other sources.

Picture of Dipl. Biol. Kathrin Muda (Foto: Uni Kassel):
www.uni-kassel.de/uni/fileadmin/datas/uni/presse/anhaenge/2014/01Muda.jpg
Picture of Prof. Dr. Friedrich W. Herberg (Foto: Uni Kassel):
www.uni-kassel.de/uni/fileadmin/datas/uni/presse/anhaenge/2014/02Herberg.jpg
Link to the study: www.pnas.org/content/early/2013/12/17/1312701111.abstract
Contact:
Prof. Dr. Friedrich W. Herberg
University of Kassel
Department of Biochemistry
Tel.: +49 561 804-4511
E-Mail: herberg@uni-kassel.de
Dipl. Biol. Kathrin Muda
University of Kassel
Department of Biochemistry
Tel.: +49 561 804-4479
E-Mail: kathrinmuda@uni-kassel.de

Sebastian Mense | idw
Further information:
http://www.uni-kassel.de
http://www.uni-kassel.de/uni/nc/universitaet/nachrichten/article/uni-kassel-molekularer-schalter-bei-parkinson-protein-entdeckt.html

More articles from Life Sciences:

nachricht Subcutaneous Administration of Multispecific Antibody Makes Tumor Treatment Faster & More Tolerable
01.07.2015 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Why human egg cells don't age well
01.07.2015 | RIKEN

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: X-rays and electrons join forces to map catalytic reactions in real-time

New technique combines electron microscopy and synchrotron X-rays to track chemical reactions under real operating conditions

A new technique pioneered at the U.S. Department of Energy's Brookhaven National Laboratory reveals atomic-scale changes during catalytic reactions in real...

Im Focus: Iron: A biological element?

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...

Im Focus: Thousands of Droplets for Diagnostics

Researchers develop new method enabling DNA molecules to be counted in just 30 minutes

A team of scientists including PhD student Friedrich Schuler from the Laboratory of MEMS Applications at the Department of Microsystems Engineering (IMTEK) of...

Im Focus: Bionic eye clinical trial results show long-term safety, efficacy vision-restoring implant

Patients using Argus II experienced significant improvement in visual function and quality of life

The three-year clinical trial results of the retinal implant popularly known as the "bionic eye," have proven the long-term efficacy, safety and reliability of...

Im Focus: Lasers for Fast Internet in Space – Space Technology from Aachen

On June 23, the second Sentinel mission was launched from the space mission launch center in Kourou. A critical component of Aachen is on board. Researchers at the Fraunhofer Institute for Laser Technology ILT and Tesat-Spacecom have jointly developed the know-how for space-qualified laser components. For the Sentinel mission the diode laser pump module of the Laser Communication Terminal LCT was planned and constructed in Aachen in cooperation with the manufacturer of the LCT, Tesat-Spacecom, and the Ferdinand Braun Institute.

After eight years of preparation, in the early morning of June 23 the time had come: in Kourou in French Guiana, the European Space Agency launched the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

World Conference on Regenerative Medicine: Abstract Submission has been extended to 24 June

16.06.2015 | Event News

MUSE hosting Europe’s largest science communication conference

11.06.2015 | Event News

 
Latest News

Offshore wind park Westermost Rough officially inaugurated

01.07.2015 | Press release

Siemens Velaro train wins "Red Dot" award

01.07.2015 | Awards Funding

Liquids on Fibers - Slipping or Flowing?

01.07.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>