Helmholtz Zentrum München receives funds from The Michael J. Fox Foundation

December 09, 2010

Starting in August 2010, an innovative project will be funded at Helmholtz Zentrum München which could pave the way for an effective therapy for PD. The aim of the project is to obtain a crystal structure of the kinase domain of the LRRK2 protein and describe its biochemical and enzymatic functions.

Professor Michael Sattler, director of the Institute of Structural Biology, Professor Marius Ueffing, head of the Department of Protein Science and Dr. Johannes Gloeckner led by Dr. Alex Burgin at Emerald Biostructures want to develop new methods in order to be able to purify and biochemically characterize larger quantities of the protein or its relevant domains. Biochemical methods shall be combined with NMR spectroscopy, small-angle X-ray scattering experiments, and ultimately X-ray crystal structure analysis in order to decode the spatial structure of the protein. "Solving the structure of the enzyme believed to be a key molecular mechanism behind Parkinson's disease could revolutionize the field," said Dr. Burgin, Emerald BioStructures.

LRRK2 (leucine-rich repeat kinase 2) is considered to be the central factor in the development of a genetic form of PD. The hyperactivity of the enzyme could lead to increased loss of neurons in the midbrain, which is characteristic of this common neurodegenerative disease.

"When the structure of LRRK2 is known, we will have legitimate hope for developing new therapeutic approaches, at least for LRRK2-associated PD," said Professor Sattler. Knowledge of the protein structure is a prerequisite for rationally developing and optimizing active substances against Parkinson's. "At the same time," he added, "we will gain new insights into how Parkinson's develops, enabling an intervention at earlier stages in the future."

Parkinson's Disease is a slowly progressing neurodegenerative disease in which dopaminergic nerve cells in midbrain die. This leads to muscular rigidity (rigor), slowness of movement (bradykinesia), muscle tremors and postural instability, apart from other disturbances. Besides the classic sporadic form (idiopathic Parkinson's syndrome), familial, genetically determined forms are also known. Type 8 is the most frequent familial form of Parkinson's Disease and is caused by mutations in the LRRK2 gene.

The LRRK2 protein consists of multiple domains and belongs to the family of protein kinases. Kinases transfer phosphate groups to target proteins and thus contribute to the control of cellular processes. The mutations of LRRK2 associated with Parkinson's Disease presumably lead to enhanced kinase activity.

About The Michael J. Fox Foundation

MJFF is dedicated to finding a cure for Parkinson's disease through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson's today. The Foundation has funded nearly $214 million in research to date. For more information, please visit www.michaeljfox.org.

Helmholtz Zentrum München is the German Research Center for Environmental Health. As leading center of Environmental Health, it focuses on chronic and complex diseases, which develop from the interaction of environmental factors and individual genetic disposition. Helmholtz Zentrum München has around 1700 staff members. The head office of the center is located in Neuherberg to the north of Munich on a 50-hectare research campus. Helmholtz Zentrum München belongs to the Helmholtz Association, Germany's largest research organization, a community of 16 scientific-technical and medical-biological research centers with a total of 30,000 staff members. - www.helmholtz-muenchen.de

Emerald BioStructures is an integrated gene-to-structure collaborative research organization specializing in drug discovery services. Emerald operates an efficient high-throughput platform leveraged for fragment-based lead discovery and structure-based drug design. Our scientists provide enabling structural insight for breakthrough drugs that are highly selective and efficacious against chosen targets. www.emeraldbiostructures.com

Helmholtz Zentrum München - German Research Center for Environmental Health

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