LRRK2 and Parkinson disease.
OBJECTIVE
To review the molecular genetics and functional biology of leucine-rich repeat kinase 2 (LRRK2) in parkinsonism and to summarize the opportunities and challenges to develop interventions for Parkinson disease (PD) based on this genetic insight.


METHODS
Publications cited are focused on LRRK2 biology between 2004 and March 2009.


METHODS
Literature selected was based on original contributions, seminal observations, and thoughtful reviews.


METHODS
Unless stated otherwise, data was primarily abstracted from peer-reviewed literature appearing on PubMed.


RESULTS
Genetic mutations that predispose PD are diagnostically useful in early or atypical presentations. The molecular pathways identified suggest therapeutic interventions for Lrrk2 and idiopathic PD and the rationale and opportunity to develop physiologically relevant biomarkers and experimental models with which to test them.


CONCLUSIONS
Both affected and asymptomatic LRRK2 carriers now provide the opportunity to define the natural history of PD. This includes the frequency, penetrance, and rate of motor symptoms, nonmotor comorbidities, and their associated biomarkers.
Dächsel
Justus C
JC
Laboratories of Neurogenetics, Department of Neuroscience, Morris K. Udall Parkinson's Disease Research Center of Excellence, Mayo Clinic, Jacksonville, Florida 32224, USA.
Farrer
Matthew J
MJ
D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000628:therapy; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012307:Risk Factors
D005819:Genetic Markers; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases