UseCases_ArguminSci_Discourse  

PubMed:20382224 JSONTXT 11 Projects

Annnotations TAB TSV DIC JSON TextAE Lectin_function IAV-Glycan

Id Subject Object Predicate Lexical cue
T1 0-130 DRI_Challenge denotes LRRK2-mediated neurodegeneration and dysfunction of dopaminergic neurons in a Caenorhabditis elegans model of Parkinson's disease.
T2 131-349 DRI_Background denotes Mutations in LRRK2 are thus far the most frequent known cause of autosomal dominant and idiopathic Parkinson's disease (PD) with prevalent mutations being found within the GTPase (R1441C/G) and kinase (G2019S) domains.
T3 350-469 DRI_Background denotes Previous in vitro studies have revealed that R1441C and G2019S mutations are associated with increased kinase activity.
T4 470-654 DRI_Outcome denotes To better understand LRRK2-linked PD pathogenesis in vivo, we have generated transgenic C. elegans overexpressing human LRRK2 wild type, R1441C and G2019S in dopaminergic (DA) neurons.
T5 655-847 DRI_Challenge denotes Overexpression of these LRRK2 proteins causes age-dependent DA neurodegeneration, behavioral deficits, and locomotor dysfunction that are accompanied by a reduction of dopamine levels in vivo.
T6 848-945 DRI_Outcome denotes In comparison, R1441C and G2019S mutants cause more severe phenotypes than the wild type protein.
T7 946-1057 DRI_Background denotes Interestingly, treatment with exogenous dopamine rescues the LRRK2-induced behavioral and locomotor phenotypes.
T8 1058-1253 DRI_Challenge denotes In contrast, expression of the GTP binding defective mutant, K1347A, or knockout of the C. elegans LRRK2 homolog, LRK-1, prevents the LRRK2-induced neurodegeneration and behavioral abnormalities.
T9 1254-1472 DRI_Outcome denotes Hence, our transgenic LRRK2 C. elegans models recapitulate key features of PD including progressive neurodegeneration, impairment of dopamine-dependent behavior and locomotor function, and reduction in dopamine levels.
T10 1473-1598 DRI_Outcome denotes Furthermore, our findings provide strong support for the critical role of GTPase/kinase activity in LRRK2-linked pathologies.
T11 1599-1734 DRI_Challenge denotes These invertebrate models will be useful for studying pathogenesis of PD and for development of potential therapeutics for the disease.