Some 5 years ago, it was first discovered that mutations in the gene encoding LRRK2 (leucine-rich repeat protein kinase 2) are tightly linked with a subset of familial PD (Parkinson's disease). Before this genetic association, LRRK2 had never been investigated biochemically. Now it is of utmost importance to establish whether LRRK2 is a bona fide kinase in vitro and in vivo and to understand how mutations of LRRK2 lead to the specific loss of dopaminergic neurons in the substantia nigra to cause PD. In spite of tremendous efforts in the research community, there is no consensus with regard to the magnitude of the enzymatic activity of LRRK2 mutant forms that segregate with PD owing, in part, to the lack of a highly sensitive kinase assay system, and it is still unclear whether an abnormal increase in kinase activity is responsible for LRRK2-associated PD. As described in this issue of the Biochemical Journal, Nichols et al. have developed an extensive set of molecular tools, including an optimized peptide substrate for determining in vitro kinase activity of LRRK2, a set of kinase inhibitors that can be used to explore LRRK2 substrate specificity and biology, a much-needed murine-specific antibody for immunoprecipation, and efficient gene-silencing approaches. In the present commentary, we discuss some of the components of this new LRRK2 biochemical toolbox and how they can be used to better understand this enigmatic kinase.
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Commentary|
October 23 2009
New biochemical approaches towards understanding the Parkinson's disease-associated kinase, LRRK2
Geou-Yarh Liou;
Geou-Yarh Liou
*Department of Cancer Biology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, U.S.A.
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Kathleen A. Gallo
Kathleen A. Gallo
1
†Department of Physiology, Michigan State University, East Lansing, MI 48824, U.S.A.
1To whom correspondence should be addressed (email gallok@msu.edu).
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Publisher: Portland Press Ltd
Received:
October 05 2009
Accepted:
October 05 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 424 (1): e1–e3.
Article history
Received:
October 05 2009
Accepted:
October 05 2009
Connected Content
A correction has been published:
Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease
Citation
Geou-Yarh Liou, Kathleen A. Gallo; New biochemical approaches towards understanding the Parkinson's disease-associated kinase, LRRK2. Biochem J 15 November 2009; 424 (1): e1–e3. doi: https://doi.org/10.1042/BJ20091540
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