LRRK2 Pathways Leading to Neurodegeneration
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Mutations in LRRK2 are associated with inherited Parkinson’s disease (PD) in a large number of families, and the genetic locus containing the LRRK2 gene contains a risk factor for sporadic PD. The LRRK2 protein contains several domains that suggest a role in cellular signaling, including a kinase domain. It is also clear that LRRK2 interacts, either physically or genetically, with several other important proteins implicated in PD, suggesting that LRRK2 may be a central player in the pathways that underlie parkinsonism. As such, LRRK2 has been proposed to be a plausible target for therapeutic intervention, with kinase inhibition being pursued most actively. However, there are still several fundamental aspects of LRRK2 biology and function that remain unresolved at this time. This review will focus on the key questions of normal function of LRRK2 and how this might be related to the pathophysiology of PD.
KeywordsAutophagy Genetics Kinase activity Mutations
This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. For reasons of space, I unfortunately was not able to quote all of the primary literature and apologize to those colleagues whose work is mentioned in other reviews and not included directly here.
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Conflict of Interest
Mark R. Cookson declares that he has no conflict of interest.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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