LRRK2 links genetic and sporadic Parkinson's disease

The past two decades in research has revealed the importance of leucine-rich repeat kinase 2 (LRRK2) in both monogenic and sporadic forms of Parkinson's disease (PD). In families, mutations in LRRK2 can cause PD with age-dependent but variable penetrance and genome-wide association studies have...

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Bibliographic Details
Published in:Biochemical Society transactions Vol. 47; no. 2; p. 651
Main Authors: Kluss, Jillian H, Mamais, Adamantios, Cookson, Mark R
Format: Journal Article
Language:English
Published: England 30.04.2019
Subjects:
Animals
Genome-Wide Association Study - methods
Humans
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - genetics
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - metabolism
Mutation - genetics
Parkinson Disease - enzymology
Parkinson Disease - genetics
Protein Serine-Threonine Kinases - genetics
leucine-rich repeat kinase
genome-wide association studies
Parkinson's disease
ISSN:1470-8752, 1470-8752
Online Access:Get more information
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Summary:The past two decades in research has revealed the importance of leucine-rich repeat kinase 2 (LRRK2) in both monogenic and sporadic forms of Parkinson's disease (PD). In families, mutations in LRRK2 can cause PD with age-dependent but variable penetrance and genome-wide association studies have found variants of the gene that are risk factors for sporadic PD. Functional studies have suggested that the common mechanism that links all disease-associated variants is that they increase LRRK2 kinase activity, albeit in different ways. Here, we will discuss the roles of LRRK2 in areas of inflammation and vesicular trafficking in the context of monogenic and sporadic PD. We will also provide a hypothetical model that links inflammation and vesicular trafficking together in an effort to outline how these pathways might interact and eventually lead to neuronal cell death. We will also highlight the translational potential of LRRK2-specific kinase inhibitors for the treatment of PD.
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ISSN:1470-8752
1470-8752
DOI:10.1042/BST20180462