The clinical picture of all patients with the LRRK2-G2019S mutation was typical for levodopa-responsive parkinsonism and age of disease onset varied widely (from 39 to 71 years).
In this brain bank-based series, LRRK2 G2019S mutation occurred in patients with parkinsonism associated with either typical brainstem LB pathology or non-specific nigral degeneration.
G2019S LRRK2 mutant fibroblasts from Parkinson's disease patients show increased sensitivity to neurotoxin 1-methyl-4-phenylpyridinium dependent of autophagy.
Low doses of paraquat and polyphenols prolong life span and locomotor activity in knock-down parkin Drosophila melanogaster exposed to oxidative stress stimuli: implication in autosomal recessive juvenile parkinsonism.
Methylmercury can induce Parkinson's-like neurotoxicity similar to 1-methyl-4- phenylpyridinium: a genomic and proteomic analysis on MN9D dopaminergic neuron cells.
A series of 106 patients with isolated or familial Parkinsonism underwent clinical evaluation and genetic testing for the LRRK2G2019S mutation which was identified in 34/106 patients (32%).
Our report adds evidence that patients with LRRK2 monogenetic Parkinsonism are well suited candidates for DBS treatment and may indicate a potential genetic predictor for positive long-term effect of STN-DBS treatment.
All patients carrying the LRRK2G2019S exhibited typical levodopa-responsive parkinsonism, and severe levodopa-induced dyskinesia was observed in the patient carrying the LRRK2 and parkin mutations.
Using Cox proportional hazard models to evaluate the risk of parkinsonism among family members of PD subjects, having a daughter with PD compared with a son was associated with increased risk of parkinsonism in the parent (HR 2.59, p=0.014) as was having a child with a LRRK2G2019S mutation (HR 3.19, p=0.003).
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.
In conclusion we show that the interaction of Lrrk1-Lrrk2 can form protein dimers and this interaction may influence the age of symptomatic manifestation in Lrrk2-parkinsonism patients.