Objective/Rationale:
LRRK2 (Leucine-Rich Repeat Kinase 2) is a protein thought to be involved in regulating signaling pathways in cells. Mutations in the gene for LRRK2 are associated with some familial forms of Parkinson’s disease (PD). A major roadblock in LRRK2 research has been the lack of appropriate tools and reagents, including high quality antibodies.
Antibodies, molecules normally used by our immune systems to recognize foreign substances, are also used by research scientists to study proteins. Antibodies can be made that recognize any protein of interest and then used to determine, for example, where that protein resides in the body or how its levels change in disease.
Because of LRRK2’s significant potential as a drug target, MJFF is making considerable investments in understanding its role in normal and Parkinson’s cellular function. Beginning in 2009, MJFF launched several efforts to develop antibodies that recognize LRRK2 in a specific and sensitive manner. The resulting antibodies are now available through Epitomics (www.epitomics.com), Neuromab (www.neuromab.org) and Covance (www.covance.com).
As a part of the Foundation’s ongoing effort to accelerate LRRK2 research, MJFF is supporting several investigators who will utilize these antibodies, as well others that are commercially available, and characterize them in a number of applications. By testing these reagents using varied methods and ensuring that this information is made widely available, scientists can quickly identify the best tool for their chosen application.
Project Description:
LRRK2 antibodies will be characterized in a number of routine laboratory applications including western blot analysis, immunohistochemistry, immunocytochemistry and immunoprecipitation. MJFF will support the following investigators in these efforts:
- Drs. Heather Melrose (Mayo Clinic Jacksonville) and Andrew West (University of Alabama)
- Dr. Dario Alessi, University of Dundee
- Dr. Deanna Benson, Mount Sinai School of Medicine
- Drs. Thomas Beach (Banner Sun Health Research Institute) and Charles White (University of Texas Southwestern Medical Center)
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Scientific progress is often delayed due to the inability of researchers to identify and access not only the reagents they need, but the corresponding information that would assist them with use of those tools. Given that the applications that will be assessed are routinely used by many investigators, by characterizing these antibodies, and making the methods available to investigators in academia and industry, MJFF strives to accelerate LRRK2 research and therapeutic development.
Anticipated Outcome:
This project will result in establishing the appropriate methods suitable for using many of the LRRK2 antibodies currently available for scientists and ensure dissemination of this information to the research community.