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 Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>