UseCases_ArguminSci_Discourse  

PubMed:22228096 JSONTXT 13 Projects

Annnotations TAB TSV DIC JSON TextAE Lectin_function IAV-Glycan

Id Subject Object Predicate Lexical cue
T1 0-89 DRI_Background denotes LRRK2 regulates mitochondrial dynamics and function through direct interaction with DLP1.
T2 90-212 DRI_Approach denotes The leucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of autosomal-dominant Parkinson disease (PD).
T3 213-293 DRI_Challenge denotes Mitochondrial dysfunction represents a critical event in the pathogenesis of PD.
T4 294-633 DRI_Outcome denotes We demonstrated that wild-type (WT) LRRK2 expression caused mitochondrial fragmentation along with increased mitochondrial dynamin-like protein (DLP1, also known as DRP1), a fission protein, which was further exacerbated by expression of PD-associated mutants (R1441C or G2019S) in both SH-SY5Y and differentiated primary cortical neurons.
T5 634-809 DRI_Outcome denotes We also found that LRRK2 interacted with DLP1, and LRRK2-DLP1 interaction was enhanced by PD-associated mutations that probably results in increased mitochondrial DLP1 levels.
T6 810-826 DRI_Background denotes Co-expression of
T7 827-854 Token_Label.OUTSIDE denotes dominant-negative DLP1 K38A
T8 855-965 DRI_Background denotes or WT Mfn2 blocked LRRK2-induced mitochondrial fragmentation, mitochondrial dysfunction and neuronal toxicity.
T9 966-1096 DRI_Background denotes Importantly, mitochondrial fragmentation and dysfunction were not observed in cells expressing either GTP-binding deficient mutant
T10 1097-1109 Token_Label.OUTSIDE denotes LRRK2 K1347A
T11 1110-1229 DRI_Background denotes or kinase-dead mutant D1994A which has minimal interaction with DLP1 and did not increase the mitochondrial DLP1 level.
T12 1230-1426 DRI_Challenge denotes We concluded that LRRK2 regulates mitochondrial dynamics by increasing mitochondrial DLP1 through its direct interaction with DLP1, and LRRK2 kinase activity plays a critical role in this process.