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PMID:16980962
| Citation |
Smith, WW, Pei, Z, Jiang, H, Dawson, VL, Dawson, TM and Ross, CA (2006) Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat. Neurosci. 9:1231-3 |
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| Abstract |
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. |
| Links |
PubMed Online version:10.1038/nn1776 |
| Keywords |
Analysis of Variance; Blotting, Western/methods; Cell Survival/drug effects; Cells, Cultured; Cerebral Cortex/cytology; Green Fluorescent Proteins/biosynthesis; Guanosine Triphosphate/metabolism; Guanosine Triphosphate/pharmacology; Humans; Immunohistochemistry/methods; In Situ Nick-End Labeling/methods; Mutagenesis/physiology; Mutation; Neuroblastoma; Neurons/drug effects; Neurons/enzymology; Neurotoxicity Syndromes/enzymology; Neurotoxicity Syndromes/genetics; Phosphotransferases/metabolism; Protein-Serine-Threonine Kinases/genetics; Transfection/methods |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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