UseCases_ArguminSci_Discourse  

PubMed:25731749 JSONTXT 15 Projects

Annnotations TAB TSV DIC JSON TextAE Lectin_function IAV-Glycan

Id Subject Object Predicate Lexical cue
T1 0-33 DRI_Challenge denotes Adenoviral-mediated expression of
T2 34-46 Token_Label.OUTSIDE denotes G2019S LRRK2
T3 47-141 DRI_Challenge denotes induces striatal pathology in a kinase-dependent manner in a rat model of Parkinson's disease.
T4 142-263 DRI_Approach denotes Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant Parkinson's disease (PD).
T5 264-316 DRI_Unspecified denotes LRRK2 contains functional GTPase and kinase domains.
T6 317-403 DRI_Background denotes The most common G2019S mutation enhances the kinase activity of LRRK2 in vitro whereas
T7 404-416 Token_Label.OUTSIDE denotes G2019S LRRK2
T8 417-494 DRI_Background denotes expression in cultured neurons induces toxicity in a kinase-dependent manner.
T9 495-582 DRI_Background denotes These observations suggest a potential role for kinase activity in LRRK2-associated PD.
T10 583-720 DRI_Approach denotes We have recently developed a novel rodent model of PD with progressive neurodegeneration induced by the adenoviral-mediated expression of
T11 721-733 Token_Label.OUTSIDE denotes G2019S LRRK2
T12 733-734 DRI_Approach denotes .
T13 735-884 DRI_Outcome denotes In the present study, we further characterize this LRRK2 model and determine the contribution of kinase activity to LRRK2-mediated neurodegeneration.
T14 885-973 DRI_Background denotes Recombinant human adenoviral vectors were employed to deliver human wild-type, G2019S or
T15 974-1009 Token_Label.OUTSIDE denotes kinase-inactive G2019S/D1994N LRRK2
T16 1010-1030 DRI_Background denotes to the rat striatum.
T17 1031-1160 DRI_Outcome denotes LRRK2-dependent pathology was assessed in the striatum, a region where LRRK2 protein is normally enriched in the mammalian brain.
T18 1161-1233 DRI_Background denotes Human LRRK2 variants are robustly expressed throughout the rat striatum.
T19 1234-1247 DRI_Challenge denotes Expression of
T20 1248-1260 Token_Label.OUTSIDE denotes G2019S LRRK2
T21 1261-1445 DRI_Challenge denotes selectively induces the accumulation of neuronal ubiquitin-positive inclusions accompanied by neurite degeneration and the altered distribution of axonal phosphorylated neurofilaments.
T22 1446-1572 DRI_Challenge denotes Importantly, the introduction of a kinase-inactive mutation (G2019S/D1994N) completely ameliorates the pathological effects of
T23 1573-1585 Token_Label.OUTSIDE denotes G2019S LRRK2
T24 1586-1683 DRI_Challenge denotes in the striatum supporting a kinase activity-dependent mechanism for this PD-associated mutation.
T25 1684-1917 DRI_Outcome denotes Collectively, our study further elucidates the pathological effects of the G2019S mutation in the mammalian brain and supports the development of kinase inhibitors as a potential therapeutic approach for treating LRRK2-associated PD.
T26 1918-2046 DRI_Outcome denotes This adenoviral rodent model provides an important tool for elucidating the molecular basis of LRRK2-mediated neurodegeneration.