PubMed_ArguminSci  

PubMed:24868377 JSONTXT 9 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 90-232 DRI_Approach denotes Mutations in Leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of sporadic and familial late onset Parkinson's disease (PD).
T2 233-334 DRI_Background denotes The G2019S common mutation has been identified about 1% of sporadic cases and 4-7% of familial cases.
T3 335-444 DRI_Background denotes Over 50 variants have since been identified in LRRK2, and at least 7 of these are confirmed to be pathogenic.
T4 445-633 DRI_Background denotes In addition to pathogenic mutations, several common polymorphisms in the LRRK2 gene (G2385R and R1628P) have been identified that may explain up to 10% of sporadic PD in Asian populations.
T5 634-737 DRI_Background denotes LRRK2 is a large complex multidomain protein with 2,527-amino-acid and the molecular weight is 286 kDa.
T6 738-743 REPLACED denotes LRRK2
T7 756-876 DRI_Background denotes protein consists of a catalytic core domain, kinase domain and a number of putative protein-protein interaction domains.
T8 877-1052 DRI_Outcome denotes LRRK2 mutations found in PD families, including the G2019S and I2020T mutations show increased intrinsic kinase activity, when assessed with myelin basic protein as substrate.
T9 1053-1286 DRI_Challenge denotes The modification of LRRK2 GTPase and kinase activity affecting residues in the ROC, COR and mitogen-activated protein kinase kinase kinases domains is believed to lead to neuronal cell death, but the pathways involved remain unclear.
T10 1287-1425 DRI_Background denotes A number of in vivo models in C. elegans, D. melanogaster and mice have been developed to study the patho/physiological function of LRRK2.
T11 1426-1668 DRI_Background denotes Based on current literature, a toxic gain of function in LRRK2 kinase activity is a possible pathophysiologic mechanism and thus inhibition of kinase activity in experimental models offers a potential therapeutic strategy for LRRK2-linked PD.