Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New drug target identified for fighting Parkinson’s disease

21.11.2005


Researchers at Johns Hopkins’ Institute for Cell Engineering (ICE) have discovered a protein that could be the best new target in the fight against Parkinson’s disease since the brain-damaging condition was first tied to loss of the brain chemical dopamine.



Over the past year, the gene for this protein, called LRRK2 (pronounced "lark-2"), had emerged as perhaps the most common genetic cause of both familial and unpredictable cases of Parkinson’s disease. Until now, however, no one knew for sure what the LRRK2 protein did in brain cells or whether interfering with it would be possible.

Now, after studying the protein in the lab, Johns Hopkins researchers report that the huge LRRK2 protein is part of a class of proteins called kinases and, like other members of the family, helps control other proteins’ activities by transferring small groups called phosphates onto them. The researchers also report that two of the known Parkinson’s-linked mutations in the LRRK2 gene increase the protein’s phosphate-adding activity. The findings appear in the current (Nov. 15) issue of the Proceedings of the National Academy of Sciences.


"We know that small molecules can interfere with this kind of activity, so LRRK2 is an obvious target for drug development," says Ted Dawson, M.D., Ph.D., co-director of the Neural Regeneration and Repair Program within ICE and a leader of the study. "This discovery is going to have a major impact on the field. It’s going to get people talking about kinase activity."

Because kinases affect a number of other proteins, LRRK2’s link to Parkinson’s may be a result of either its own activity or a shift in the activities of one or more "downstream" proteins.

"The next step is to prove that LRRK2 overactivity results in the death of brain cells that produce dopamine, the defining pathology of Parkinson’s disease, and to figure out how it does so," says Dawson, who cautions that the large size of the LRRK2 gene and protein could make clinical application of the Hopkins discovery years away.

"For example, we would want to isolate the active part of the LRRK2 protein and use that more manageable part to screen for molecules that would block its activity. But what takes us a second to think of could take four or five months to do," says Dawson. "These things may not come as fast as the field wants."

The LRRK2 protein, sometimes called dardarin, is 2,527 building blocks long. In contrast, the alpha-synuclein protein, the first to be linked to Parkinson’s disease, is only 140 building blocks long. The parkin protein, linked to more cases of familial Parkinson’s disease than any other to date (although LRRK2 is likely to break that record), is considered "big" at 465 building blocks long.

Undaunted by the size of the LRRK2 gene and protein, Andrew West, Ph.D., a postdoctoral fellow and co-first author of the paper, spent months extracting the full-length gene from human brain samples and developing reliable experiments to test how mutations affected LRRK2’s activity. Co-first author Darren Moore, Ph.D., also a postdoctoral fellow, built the tools to get bacteria to make mounds of LRRK2 protein and two mutant versions and also tracked down the LRRK2 protein’s location inside cells.

The research team’s experiments showed that the LRRK2 protein, in addition to its role as a kinase, actually sits on mitochondria, cells’ energy-producing factories, where it likely interacts with a complex of proteins whose failure has also been implicated in Parkinson’s disease.

Mutations in LRRK2 were first tied to Parkinson’s disease in 2004 and to date explain perhaps 5 percent to 6 percent of familial Parkinson’s disease (specifically so-called autosomal dominant cases, in which inheriting a single faulty copy of the gene results in disease) and roughly 1 percent of Parkinson’s disease in which there is no family history. But few of the gene’s genetic regions have been analyzed in depth.

"As researchers comb through the rest of the LRRK2 gene, it seems likely that more mutations will be found and that it will be tied to more varieties of the disease," says Dawson. What’s known about LRRK2 so far suggests that it might connect diseases long thought to be distinct, particularly Parkinson’s disease and conditions known as "diffuse Lewy body disease," named for the bundles of certain proteins that build up inside cells in the brain in affected people. As a result, studying LRRK2 might improve understanding of and eventually treatment for more than just Parkinson’s disease itself, Dawson says.

Joanna Downer | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Individualized fiber components for the world market

23.06.2017 | Physics and Astronomy

How brains surrender to sleep

23.06.2017 | Life Sciences

Can we see monkeys from space? Emerging technologies to map biodiversity

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>