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Neurodegener Dis. 2008;5(3-4):182-5. doi: 10.1159/000113697. Epub 2008 Mar 6.

Investigating convergent actions of genes linked to familial Parkinson's disease.

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  • 1Department of Pharmacology, Boston University School of Medicine, Boston, Mass. 02118-2526, USA.



Mutations in LRRK2 are among the most frequent genetic changes identified in Parkinson's disease (PD), but how LRRK2 contributes to the pathophysiology of PD is not known.


To investigate how expressing wild-type or G2019S LRRK2 modifies cellular responses to rotenone, a mitochondrial toxin.


We investigated the vulnerability to mitochondrial toxins in Caenorhabditis elegans expressing wild-type or G2019S LRRK2.


We observed a powerful role for LRRK2 in mitochondrial biology. Overexpressing LRRK2 strongly protects C. elegans against rotenone toxicity. The G2019S LRRK2 construct also protected LRRK2 against rotenone, but to a lesser degree than wild-type LRRK2. Knockdown of lrk-1 potentiated rotenone toxicity.


These data suggest that LRRK1/2 regulate mitochondrial physiology.

2008 S. Karger AG, Basel

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