UseCases_ArguminSci_Discourse  

PubMed:22736029 JSONTXT 13 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 0-100 DRI_Approach denotes G2019S leucine-rich repeat kinase 2 causes uncoupling protein-mediated mitochondrial depolarization.
T2 101-287 DRI_Challenge denotes The G2019S leucine rich repeat kinase 2 (LRRK2) mutation is the most common genetic cause of Parkinson's disease (PD), clinically and pathologically indistinguishable from idiopathic PD.
T3 288-457 DRI_Background denotes Mitochondrial abnormalities are a common feature in PD pathogenesis and we have investigated the impact of G2019S mutant LRRK2 expression on mitochondrial bioenergetics.
T4 458-584 DRI_Background denotes LRRK2 protein expression was detected in fibroblasts and lymphoblasts at levels higher than those observed in the mouse brain.
T5 585-600 DRI_Background denotes The presence of
T6 601-613 Token_Label.OUTSIDE denotes G2019S LRRK2
T7 614-673 DRI_Background denotes mutation did not influence LRRK2 expression in fibroblasts.
T8 674-704 DRI_Outcome denotes However, the expression of the
T9 705-717 Token_Label.OUTSIDE denotes G2019S LRRK2
T10 718-815 DRI_Outcome denotes mutation in both fibroblast and neuroblastoma cells was associated with mitochondrial uncoupling.
T11 816-966 DRI_Background denotes This was characterized by decreased mitochondrial membrane potential and increased oxygen utilization under basal and oligomycin-inhibited conditions.
T12 967-1064 DRI_Approach denotes This resulted in a decrease in cellular ATP levels consistent with compromised cellular function.
T13 1065-1216 DRI_Background denotes This uncoupling of mitochondrial oxidative phosphorylation was associated with a cell-specific increase in uncoupling protein (UCP) 2 and 4 expression.
T14 1217-1339 DRI_Background denotes Restoration of mitochondrial membrane potential by the UCP inhibitor genipin confirmed the role of UCPs in this mechanism.
T15 1340-1343 DRI_Background denotes The
T16 1344-1364 Token_Label.OUTSIDE denotes G2019S LRRK2-induced
T17 1365-1422 DRI_Background denotes mitochondrial uncoupling and UCP4 mRNA up-regulation were
T18 1423-1445 Token_Label.OUTSIDE denotes LRRK2 kinase-dependent
T19 1445-1525 DRI_Background denotes , whereas endogenous LRRK2 levels were required for constitutive UCP expression.
T20 1526-1608 DRI_Challenge denotes We propose that normal mitochondrial function was deregulated by the expression of
T21 1609-1621 Token_Label.OUTSIDE denotes G2019S LRRK2
T22 1622-1782 DRI_Challenge denotes in a kinase-dependent mechanism that is a modification of the normal LRRK2 function, and this leads to the vulnerability of selected neuronal populations in PD.