Journal
NATURE NEUROSCIENCE
Volume 9, Issue 10, Pages 1231-1233Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn1776
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Funding
- NINDS NIH HHS [NS38377, R21NS055684-01] Funding Source: Medline
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Mutations in the the leucine-rich repeat kinase-2 (LRRK2) gene cause autosomal- dominant Parkinson disease and some cases of sporadic Parkinson disease. Here we found that LRRK2 kinase activity was regulated by GTP via the intrinsic GTPase Roc domain, and alterations of LRRK2 protein that reduced kinase activity of mutant LRRK2 correspondingly reduced neuronal toxicity. These data elucidate the pathogenesis of LRRK2-linked Parkinson disease, potentially illuminate mechanisms of sporadic Parkinson disease and suggest therapeutic targets.
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