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Role of LRRK2 kinase dysfunction in Parkinson disease

Published online by Cambridge University Press:  13 June 2011

Azad Kumar
Affiliation:
Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Mark R. Cookson*
Affiliation:
Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
*
*Corresponding author: Mark R. Cookson, Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda, MD 20892-3707, USA. E-mail: cookson@mail.nih.gov

Abstract

Parkinson disease is a common and usually sporadic neurodegenerative disorder. However, a subset of cases are inherited and, of these, mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most frequent genetic cause of disease. Here, we will discuss recent progress in understanding how LRRK2 mutations lead to disease and how this might have therapeutic implications. The effect of mutations on LRRK2 enzyme function provides clues as to which functions of the protein are important to disease. Recent work has focused on the kinase and GTP-binding domains of LRRK2, and it is assumed that these will be therapeutically important, although there is a substantial amount of work to be done to address this hypothesis.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2011. This is a work of the US Government and is not subject to copyright protection in the USA

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References

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Further reading, resources and contacts

Cookson, M.R. (2010). The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease. Nature Reviews Neuroscience 11, 791-797CrossRefGoogle ScholarPubMed
Greggio, E. and Cookson, M.R. (2009) Leucine-rich repeat kinase 2 mutations and Parkinson's disease: three questions. ASN Neuro 1, e0002CrossRefGoogle ScholarPubMed
General information about PD research can be found at PDOnline: http://www.pdonlineresearch.org/.Google Scholar
Up-to-date information on inherited forms of PD can be obtained from the OMIM (online inheritance in man) website: http://www.ncbi.nlm.nih.gov/omim.Google Scholar
Additional data on the association of specific genetic variants with PD can be found at pdgene: http://www.pdgene.org.Google Scholar
General information about PD research can be found at PDOnline: http://www.pdonlineresearch.org/.Google Scholar
Up-to-date information on inherited forms of PD can be obtained from the OMIM (online inheritance in man) website: http://www.ncbi.nlm.nih.gov/omim.Google Scholar
Additional data on the association of specific genetic variants with PD can be found at pdgene: http://www.pdgene.org.Google Scholar