UseCases_ArguminSci_Discourse  

PubMed:21972245 JSONTXT 15 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 0-160 DRI_Background denotes Transcriptional responses to loss or gain of function of the leucine-rich repeat kinase 2 (LRRK2) gene uncover biological processes modulated by LRRK2 activity.
T2 161-341 DRI_Approach denotes Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most common genetic cause of Parkinson's disease (PD) and cause both autosomal dominant familial and sporadic PD.
T3 342-428 DRI_Background denotes Currently, the physiological and pathogenic activities of LRRK2 are poorly understood.
T4 429-708 DRI_Background denotes To decipher the biological functions of LRRK2, including the genes and pathways modulated by LRRK2 kinase activity in vivo, we assayed genome-wide mRNA expression in the brain and peripheral tissues from LRRK2 knockout (KO) and kinase hyperactive G2019S (G2019S) transgenic mice.
T5 709-908 DRI_Outcome denotes Subtle but significant differences in mRNA expression were observed relative to wild-type (WT) controls in the cortex, striatum and kidney of KO animals, but only in the striatum in the G2019S model.
T6 909-1167 DRI_Background denotes In contrast, robust, consistent and highly significant differences were identified by the direct comparison of KO and G2019S profiles in the cortex, striatum, kidney and muscle, indicating opposite effects on mRNA expression by the two models relative to WT.
T7 1168-1265 DRI_Background denotes Ribosomal and glycolytic biological functions were consistently and significantly up-regulated in
T8 1266-1278 Token_Label.OUTSIDE denotes LRRK2 G2019S
T9 1279-1310 DRI_Background denotes compared with LRRK2 KO tissues.
T10 1311-1451 DRI_Background denotes Genes involved in membrane-bound organelles, oxidative phosphorylation, mRNA processing and the endoplasmic reticulum were down-regulated in
T11 1452-1464 Token_Label.OUTSIDE denotes LRRK2 G2019S
T12 1465-1487 DRI_Background denotes mice compared with KO.
T13 1488-1620 DRI_Outcome denotes We confirmed the expression patterns of 35 LRRK2-regulated genes using quantitative reverse transcription polymerase chain reaction.
T14 1621-1903 DRI_Background denotes These findings provide the first description of the transcriptional responses to genetically modified LRRK2 activity and provide preclinical target engagement and/or pharmacodynamic biomarker strategies for LRRK2 and may inform future therapeutic strategies for LRRK2-associated PD.