UseCases_ArguminSci_Discourse  

PubMed:26546614 JSONTXT 13 Projects

Annnotations TAB TSV DIC JSON TextAE Lectin_function IAV-Glycan

Id Subject Object Predicate Lexical cue
T1 0-77 DRI_Background denotes 14-3-3 Proteins regulate mutant LRRK2 kinase activity and neurite shortening.
T2 78-244 DRI_Approach denotes Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common known cause of inherited Parkinson's disease (PD), and LRRK2 is a risk factor for idiopathic PD.
T3 245-300 DRI_Background denotes How LRRK2 function is regulated is not well understood.
T4 301-459 DRI_Background denotes Recently, the highly conserved 14-3-3 proteins, which play a key role in many cellular functions including cell death, have been shown to interact with LRRK2.
T5 460-580 DRI_Approach denotes In this study, we investigated whether 14-3-3s can regulate mutant LRRK2-induced neurite shortening and kinase activity.
T6 581-730 DRI_Background denotes In the presence of 14-3-3θ overexpression, neurite length of primary neurons from BAC transgenic G2019S-LRRK2 mice returned back to wild-type levels.
T7 731-852 DRI_Background denotes Similarly, 14-3-3θ overexpression reversed neurite shortening in neuronal cultures from BAC transgenic R1441G-LRRK2 mice.
T8 853-926 DRI_Background denotes Conversely, inhibition of 14-3-3s by the pan-14-3-3 inhibitor difopein or
T9 927-952 Token_Label.OUTSIDE denotes dominant-negative 14-3-3θ
T10 953-1009 DRI_Background denotes further reduced neurite length in G2019S-LRRK2 cultures.
T11 1010-1147 DRI_Background denotes Since G2019S-LRRK2 toxicity is likely mediated through increased kinase activity, we examined 14-3-3θ's effects on LRRK2 kinase activity.
T12 1148-1276 DRI_Background denotes 14-3-3θ overexpression reduced the kinase activity of G2019S-LRRK2, while difopein promoted the kinase activity of G2019S-LRRK2.
T13 1277-1378 DRI_Challenge denotes The ability of 14-3-3θ to reduce LRRK2 kinase activity required direct binding of 14-3-3θ with LRRK2.
T14 1379-1494 DRI_Background denotes The potentiation of neurite shortening by difopein in G2019S-LRRK2 neurons was reversed by LRRK2 kinase inhibitors.
T15 1495-1634 DRI_Approach denotes Taken together, we conclude that 14-3-3θ can regulate LRRK2 and reduce the toxicity of mutant LRRK2 through a reduction of kinase activity.