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BMC Medicine
Published in: BMC Medicine 1/2012

Open Access 01-12-2012 | Minireview

Is inhibition of kinase activity the only therapeutic strategy for LRRK2-associated Parkinson's disease?

Authors: Iakov N Rudenko, Ruth Chia, Mark R Cookson

Published in: BMC Medicine | Issue 1/2012

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Abstract

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a common cause of familial Parkinson's disease (PD). Variation around the LRRK2 locus also contributes to the risk of sporadic PD. The LRRK2 protein contains a central catalytic region, and pathogenic mutations cluster in the Ras of complex protein C terminus of Ras of complex protein (mutations N1437H, R1441G/C and Y1699C) and kinase (G2019S and I2020T) domains. Much attention has been focused on the kinase domain, because kinase-dead versions of mutant LRRK2 are less toxic than kinase-active versions of the same proteins. Furthermore, kinase inhibitors may be able to mimic this effect in mouse models, although the currently tested inhibitors are not completely specific. In this review, we discuss the recent progress in the development of specific LRRK2 kinase inhibitors. We also discuss non-kinase-based therapeutic strategies for LRRK2-associated PD as it is possible that different approaches may be needed for different mutations.
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Metadata
Title
Is inhibition of kinase activity the only therapeutic strategy for LRRK2-associated Parkinson's disease?
Authors
Iakov N Rudenko
Ruth Chia
Mark R Cookson
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2012
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-10-20

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