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Leucine-Rich Repeat Kinase 2 Mutations and Parkinson's Disease: Three Questions

Open access
Greggio, Elisa, Cookson, Mark R·2009·ASN Neuro

Abstract

Mutations in the gene encoding LRRK2 (leucine-rich repeat kinase 2) were first identified in 2004 and have since been shown to be the single most common cause of inherited Parkinson's disease. The protein is a large GTP-regulated serine/threonine kinase that additionally contains several protein-protein interaction domains. In the present review, we discuss three important, but unresolved, questions concerning LRRK2. We first ask: what is the normal function of LRRK2? Related to this, we discuss the evidence of LRRK2 activity as a GTPase and as a kinase and the available data on protein-protein interactions. Next we raise the question of how mutations affect LRRK2 function, focusing on some slightly controversial results related to the kinase activity of the protein in a variety of in vitro systems. Finally, we discuss what the possible mechanisms are for LRRK2-mediated neurotoxicity, in the context of known activities of the protein.

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Metadata

Authors
Greggio, E., & Cookson, M. R.
Venue
ASN Neuro
Published
2009-01
Volume
1
Issue
1
ISSN
1759-0914 (ISSN-L)
OpenAlex
W2072216745
Cited by
272
References
4
FWCI
18.38
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Leucine-Rich Repeat Kinase 2 Mutations and Parkinson's Disease: Three Questions. https://app.cochat.ai/papers/10.1042/an20090007
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Greggio, E., & Cookson, M. R. (2009). Leucine-Rich Repeat Kinase 2 Mutations and Parkinson's Disease: Three Questions. ASN Neuro. https://doi.org/10.1042/an20090007

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