PubMed_ArguminSci  

PubMed:25731749 JSONTXT 15 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 142-263 DRI_Approach denotes Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant Parkinson's disease (PD).
T2 317-403 DRI_Background denotes The most common G2019S mutation enhances the kinase activity of LRRK2 in vitro whereas
T3 417-494 DRI_Background denotes expression in cultured neurons induces toxicity in a kinase-dependent manner.
T4 495-582 DRI_Background denotes These observations suggest a potential role for kinase activity in LRRK2-associated PD.
T5 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
T6 733-734 DRI_Approach denotes .
T7 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.
T8 885-973 DRI_Background denotes Recombinant human adenoviral vectors were employed to deliver human wild-type, G2019S or
T9 1010-1030 DRI_Background denotes to the rat striatum.
T10 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.
T11 1161-1233 DRI_Background denotes Human LRRK2 variants are robustly expressed throughout the rat striatum.
T12 1234-1247 DRI_Challenge denotes Expression of
T13 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.
T14 1446-1572 DRI_Challenge denotes Importantly, the introduction of a kinase-inactive mutation (G2019S/D1994N) completely ameliorates the pathological effects of
T15 1586-1683 DRI_Challenge denotes in the striatum supporting a kinase activity-dependent mechanism for this PD-associated mutation.
T16 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.
T17 1918-2046 DRI_Outcome denotes This adenoviral rodent model provides an important tool for elucidating the molecular basis of LRRK2-mediated neurodegeneration.