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):
Sebastian Mense | idw
Novel 'repair system' discovered in algae may yield new tools for biotechnology
29.07.2016 | Boyce Thompson Institute
Molecular troublemakers instead of antibiotics?
29.07.2016 | Christian-Albrechts-Universität zu Kiel
Transparent electronics devices are present in today’s thin film displays, solar cells, and touchscreens. The future will bring flexible versions of such devices. Their production requires printable materials that are transparent and remain highly conductive even when deformed. Researchers at INM – Leibniz Institute for New Materials have combined a new self-assembling nano ink with an imprint process to create flexible conductive grids with a resolution below one micrometer.
To print the grids, an ink of gold nanowires is applied to a substrate. A structured stamp is pressed on the substrate and forces the ink into a pattern. “The...
A new Fraunhofer MEVIS method conveys medical interrelationships quickly and intuitively with innovative visualization technology
On the monitor, a brain spins slowly and can be examined from every angle. Suddenly, some sections start glowing, first on the side and then the entire back of...
Researchers at the U.S. Department of Energy's (DOE) Ames Laboratory have discovered an unusual property of purple bronze that may point to new ways to achieve high temperature superconductivity.
While studying purple bronze, a molybdenum oxide, researchers discovered an unconventional charge density wave on its surface.
Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.
Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...
Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases
Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...
29.07.2016 | Event News
15.07.2016 | Event News
15.07.2016 | Event News
29.07.2016 | Power and Electrical Engineering
29.07.2016 | Life Sciences
29.07.2016 | Event News