PubMed:25731749
Annnotations
PubTator4TogoVar
Id | Subject | Object | Predicate | Lexical cue | proteinmutation |
---|---|---|---|---|---|
25731749_0 | 34-40 | ProteinMutation | denotes | G2019S | rs34637584 |
25731749_1 | 333-339 | ProteinMutation | denotes | G2019S | rs34637584 |
25731749_2 | 404-410 | ProteinMutation | denotes | G2019S | rs34637584 |
25731749_3 | 721-727 | ProteinMutation | denotes | G2019S | rs34637584 |
25731749_4 | 964-970 | ProteinMutation | denotes | G2019S | rs34637584 |
25731749_5 | 990-996 | ProteinMutation | denotes | G2019S | rs34637584 |
25731749_6 | 1248-1254 | ProteinMutation | denotes | G2019S | rs34637584 |
25731749_7 | 1507-1513 | ProteinMutation | denotes | G2019S | rs34637584 |
25731749_8 | 1573-1579 | ProteinMutation | denotes | G2019S | rs34637584 |
25731749_9 | 1759-1765 | ProteinMutation | denotes | G2019S | rs34637584 |
c_corpus
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T1 | 41-46 | PR:Q5S006 | denotes | LRRK2 |
T2 | 41-46 | PR:000003033 | denotes | LRRK2 |
T3 | 41-46 | PR:Q5S007 | denotes | LRRK2 |
T5 | 108-111 | PR:P63003-1 | denotes | rat |
T6 | 108-111 | PR:Q2G0B1 | denotes | rat |
T7 | 108-111 | PR:Q8VHJ4 | denotes | rat |
T4 | 108-111 | 10116 | denotes | rat |
T8 | 108-111 | D051381 | denotes | rat |
T13 | 121-140 | D010300 | denotes | Parkinson's disease |
T14 | 121-140 | D010300 | denotes | Parkinson's disease |
T18 | 159-166 | 6308 | denotes | leucine |
T19 | 159-166 | SO:0001437 | denotes | leucine |
T17 | 159-166 | CHEBI:15603 | denotes | leucine |
T20 | 159-166 | D007930 | denotes | leucine |
T21 | 159-166 | CHEBI:25017 | denotes | leucine |
T22 | 159-166 | D007930 | denotes | leucine |
T23 | 172-178 | SO:0001068 | denotes | repeat |
T24 | 189-194 | PR:Q5S006 | denotes | LRRK2 |
T25 | 189-194 | PR:000003033 | denotes | LRRK2 |
T26 | 189-194 | PR:Q5S007 | denotes | LRRK2 |
T27 | 196-200 | SO:0000704 | denotes | gene |
T28 | 207-217 | D000067562 | denotes | late-onset |
T29 | 207-217 | D000067562 | denotes | late-onset |
T30 | 219-237 | C566739 | denotes | autosomal dominant |
T35 | 238-257 | D010300 | denotes | Parkinson's disease |
T36 | 238-257 | D010300 | denotes | Parkinson's disease |
T39 | 264-269 | PR:Q5S006 | denotes | LRRK2 |
T40 | 264-269 | PR:000003033 | denotes | LRRK2 |
T41 | 264-269 | PR:Q5S007 | denotes | LRRK2 |
T42 | 290-296 | D020558 | denotes | GTPase |
T43 | 340-348 | SO:0000109 | denotes | mutation |
T44 | 362-377 | GO:0016301 | denotes | kinase activity |
T45 | 381-386 | PR:Q5S006 | denotes | LRRK2 |
T46 | 381-386 | PR:000003033 | denotes | LRRK2 |
T47 | 381-386 | PR:Q5S007 | denotes | LRRK2 |
T48 | 411-416 | PR:Q5S006 | denotes | LRRK2 |
T49 | 411-416 | PR:000003033 | denotes | LRRK2 |
T50 | 411-416 | PR:Q5S007 | denotes | LRRK2 |
T51 | 543-558 | GO:0016301 | denotes | kinase activity |
T52 | 562-567 | PR:Q5S006 | denotes | LRRK2 |
T53 | 562-567 | PR:000003033 | denotes | LRRK2 |
T54 | 562-567 | PR:Q5S007 | denotes | LRRK2 |
T55 | 618-624 | D012377 | denotes | rodent |
T56 | 728-733 | PR:Q5S006 | denotes | LRRK2 |
T57 | 728-733 | PR:000003033 | denotes | LRRK2 |
T58 | 728-733 | PR:Q5S007 | denotes | LRRK2 |
T59 | 786-791 | PR:Q5S006 | denotes | LRRK2 |
T60 | 786-791 | PR:000003033 | denotes | LRRK2 |
T61 | 786-791 | PR:Q5S007 | denotes | LRRK2 |
T62 | 832-847 | GO:0016301 | denotes | kinase activity |
T63 | 851-856 | PR:Q5S006 | denotes | LRRK2 |
T64 | 851-856 | PR:000003033 | denotes | LRRK2 |
T65 | 851-856 | PR:Q5S007 | denotes | LRRK2 |
T66 | 897-902 | D006801 | denotes | human |
T67 | 947-952 | D006801 | denotes | human |
T68 | 953-962 | SO:0000817 | denotes | wild-type |
T69 | 1004-1009 | PR:Q5S006 | denotes | LRRK2 |
T70 | 1004-1009 | PR:000003033 | denotes | LRRK2 |
T71 | 1004-1009 | PR:Q5S007 | denotes | LRRK2 |
T73 | 1017-1020 | PR:P63003-1 | denotes | rat |
T74 | 1017-1020 | PR:Q2G0B1 | denotes | rat |
T75 | 1017-1020 | PR:Q8VHJ4 | denotes | rat |
T72 | 1017-1020 | 10116 | denotes | rat |
T76 | 1017-1020 | D051381 | denotes | rat |
T77 | 1021-1029 | UBERON:0002435 | denotes | striatum |
T78 | 1021-1029 | UBERON:0005383 | denotes | striatum |
T79 | 1031-1036 | PR:Q5S006 | denotes | LRRK2 |
T80 | 1031-1036 | PR:000003033 | denotes | LRRK2 |
T81 | 1031-1036 | PR:Q5S007 | denotes | LRRK2 |
T82 | 1077-1085 | UBERON:0002435 | denotes | striatum |
T83 | 1077-1085 | UBERON:0005383 | denotes | striatum |
T84 | 1102-1107 | PR:Q5S006 | denotes | LRRK2 |
T85 | 1102-1107 | PR:000003033 | denotes | LRRK2 |
T86 | 1102-1107 | PR:Q5S007 | denotes | LRRK2 |
T87 | 1102-1115 | D000071158 | denotes | LRRK2 protein |
T91 | 1108-1115 | PR:000000001 | denotes | protein |
T88 | 1108-1115 | GO:0003675 | denotes | protein |
T92 | 1108-1115 | SO:0000104 | denotes | protein |
T93 | 1154-1159 | UBERON:6110636 | denotes | brain |
T94 | 1154-1159 | UBERON:0000955 | denotes | brain |
T95 | 1161-1166 | D006801 | denotes | Human |
T96 | 1167-1172 | PR:Q5S006 | denotes | LRRK2 |
T97 | 1167-1172 | PR:000003033 | denotes | LRRK2 |
T98 | 1167-1172 | PR:Q5S007 | denotes | LRRK2 |
T100 | 1220-1223 | PR:P63003-1 | denotes | rat |
T101 | 1220-1223 | PR:Q2G0B1 | denotes | rat |
T102 | 1220-1223 | PR:Q8VHJ4 | denotes | rat |
T99 | 1220-1223 | 10116 | denotes | rat |
T103 | 1220-1223 | D051381 | denotes | rat |
T104 | 1224-1232 | UBERON:0002435 | denotes | striatum |
T105 | 1224-1232 | UBERON:0005383 | denotes | striatum |
T106 | 1255-1260 | PR:Q5S006 | denotes | LRRK2 |
T107 | 1255-1260 | PR:000003033 | denotes | LRRK2 |
T108 | 1255-1260 | PR:Q5S007 | denotes | LRRK2 |
T109 | 1310-1319 | P68197 | denotes | ubiquitin |
T110 | 1310-1319 | P84589 | denotes | ubiquitin |
T111 | 1310-1319 | P19848 | denotes | ubiquitin |
T113 | 1310-1319 | Q8SWD4 | denotes | ubiquitin |
T114 | 1310-1319 | P62975 | denotes | ubiquitin |
T115 | 1310-1319 | P69310 | denotes | ubiquitin |
T116 | 1310-1319 | PR:000035728 | denotes | ubiquitin |
T117 | 1310-1319 | P69317 | denotes | ubiquitin |
T118 | 1310-1319 | Q865C5 | denotes | ubiquitin |
T120 | 1310-1319 | P69313 | denotes | ubiquitin |
T122 | 1310-1319 | P69326 | denotes | ubiquitin |
T119 | 1310-1319 | D025801 | denotes | ubiquitin |
T121 | 1310-1319 | CHEBI:17471 | denotes | ubiquitin |
T112 | 1310-1319 | GO:0031386 | denotes | ubiquitin |
T123 | 1355-1362 | GO:0043005 | denotes | neurite |
T124 | 1497-1505 | SO:0000109 | denotes | mutation |
T125 | 1580-1585 | PR:Q5S006 | denotes | LRRK2 |
T126 | 1580-1585 | PR:000003033 | denotes | LRRK2 |
T127 | 1580-1585 | PR:Q5S007 | denotes | LRRK2 |
T128 | 1593-1601 | UBERON:0002435 | denotes | striatum |
T129 | 1593-1601 | UBERON:0005383 | denotes | striatum |
T130 | 1615-1630 | GO:0016301 | denotes | kinase activity |
T131 | 1674-1682 | SO:0000109 | denotes | mutation |
T132 | 1766-1774 | SO:0000109 | denotes | mutation |
T133 | 1792-1797 | UBERON:6110636 | denotes | brain |
T134 | 1792-1797 | UBERON:0000955 | denotes | brain |
T135 | 1837-1847 | CHEBI:35222 | denotes | inhibitors |
T136 | 1897-1902 | PR:Q5S006 | denotes | LRRK2 |
T137 | 1897-1902 | PR:000003033 | denotes | LRRK2 |
T138 | 1897-1902 | PR:Q5S007 | denotes | LRRK2 |
T139 | 1934-1940 | D012377 | denotes | rodent |
T140 | 2013-2018 | PR:Q5S006 | denotes | LRRK2 |
T141 | 2013-2018 | PR:000003033 | denotes | LRRK2 |
T142 | 2013-2018 | PR:Q5S007 | denotes | LRRK2 |
PubmedHPO
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T1 | 219-237 | HP_0000006 | denotes | autosomal dominant |
T2 | 238-247 | HP_0001300 | denotes | Parkinson |
T3 | 642-671 | HP_0002344 | denotes | progressive neurodegeneration |
T4 | 654-671 | HP_0002180 | denotes | neurodegeneration |
T5 | 866-883 | HP_0002180 | denotes | neurodegeneration |
T6 | 2028-2045 | HP_0002180 | denotes | neurodegeneration |
UseCases_ArguminSci_Discourse
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T1 | 0-33 | DRI_Challenge | denotes | Adenoviral-mediated expression of |
T2 | 34-46 | Token_Label.OUTSIDE | denotes | G2019S LRRK2 |
T3 | 47-141 | DRI_Challenge | denotes | induces striatal pathology in a kinase-dependent manner in a rat model of Parkinson's disease. |
T4 | 142-263 | DRI_Approach | denotes | Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant Parkinson's disease (PD). |
T5 | 264-316 | DRI_Unspecified | denotes | LRRK2 contains functional GTPase and kinase domains. |
T6 | 317-403 | DRI_Background | denotes | The most common G2019S mutation enhances the kinase activity of LRRK2 in vitro whereas |
T7 | 404-416 | Token_Label.OUTSIDE | denotes | G2019S LRRK2 |
T8 | 417-494 | DRI_Background | denotes | expression in cultured neurons induces toxicity in a kinase-dependent manner. |
T9 | 495-582 | DRI_Background | denotes | These observations suggest a potential role for kinase activity in LRRK2-associated PD. |
T10 | 583-720 | DRI_Approach | denotes | We have recently developed a novel rodent model of PD with progressive neurodegeneration induced by the adenoviral-mediated expression of |
T11 | 721-733 | Token_Label.OUTSIDE | denotes | G2019S LRRK2 |
T12 | 733-734 | DRI_Approach | denotes | . |
T13 | 735-884 | DRI_Outcome | denotes | In the present study, we further characterize this LRRK2 model and determine the contribution of kinase activity to LRRK2-mediated neurodegeneration. |
T14 | 885-973 | DRI_Background | denotes | Recombinant human adenoviral vectors were employed to deliver human wild-type, G2019S or |
T15 | 974-1009 | Token_Label.OUTSIDE | denotes | kinase-inactive G2019S/D1994N LRRK2 |
T16 | 1010-1030 | DRI_Background | denotes | to the rat striatum. |
T17 | 1031-1160 | DRI_Outcome | denotes | LRRK2-dependent pathology was assessed in the striatum, a region where LRRK2 protein is normally enriched in the mammalian brain. |
T18 | 1161-1233 | DRI_Background | denotes | Human LRRK2 variants are robustly expressed throughout the rat striatum. |
T19 | 1234-1247 | DRI_Challenge | denotes | Expression of |
T20 | 1248-1260 | Token_Label.OUTSIDE | denotes | G2019S LRRK2 |
T21 | 1261-1445 | DRI_Challenge | denotes | selectively induces the accumulation of neuronal ubiquitin-positive inclusions accompanied by neurite degeneration and the altered distribution of axonal phosphorylated neurofilaments. |
T22 | 1446-1572 | DRI_Challenge | denotes | Importantly, the introduction of a kinase-inactive mutation (G2019S/D1994N) completely ameliorates the pathological effects of |
T23 | 1573-1585 | Token_Label.OUTSIDE | denotes | G2019S LRRK2 |
T24 | 1586-1683 | DRI_Challenge | denotes | in the striatum supporting a kinase activity-dependent mechanism for this PD-associated mutation. |
T25 | 1684-1917 | DRI_Outcome | denotes | Collectively, our study further elucidates the pathological effects of the G2019S mutation in the mammalian brain and supports the development of kinase inhibitors as a potential therapeutic approach for treating LRRK2-associated PD. |
T26 | 1918-2046 | DRI_Outcome | denotes | This adenoviral rodent model provides an important tool for elucidating the molecular basis of LRRK2-mediated neurodegeneration. |
PubMed_ArguminSci
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
T1 | 142-263 | DRI_Approach | denotes | Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant Parkinson's disease (PD). |
T2 | 317-403 | DRI_Background | denotes | The most common G2019S mutation enhances the kinase activity of LRRK2 in vitro whereas |
T3 | 417-494 | DRI_Background | denotes | expression in cultured neurons induces toxicity in a kinase-dependent manner. |
T4 | 495-582 | DRI_Background | denotes | These observations suggest a potential role for kinase activity in LRRK2-associated PD. |
T5 | 583-720 | DRI_Approach | denotes | We have recently developed a novel rodent model of PD with progressive neurodegeneration induced by the adenoviral-mediated expression of |
T6 | 733-734 | DRI_Approach | denotes | . |
T7 | 735-884 | DRI_Outcome | denotes | In the present study, we further characterize this LRRK2 model and determine the contribution of kinase activity to LRRK2-mediated neurodegeneration. |
T8 | 885-973 | DRI_Background | denotes | Recombinant human adenoviral vectors were employed to deliver human wild-type, G2019S or |
T9 | 1010-1030 | DRI_Background | denotes | to the rat striatum. |
T10 | 1031-1160 | DRI_Outcome | denotes | LRRK2-dependent pathology was assessed in the striatum, a region where LRRK2 protein is normally enriched in the mammalian brain. |
T11 | 1161-1233 | DRI_Background | denotes | Human LRRK2 variants are robustly expressed throughout the rat striatum. |
T12 | 1234-1247 | DRI_Challenge | denotes | Expression of |
T13 | 1261-1445 | DRI_Challenge | denotes | selectively induces the accumulation of neuronal ubiquitin-positive inclusions accompanied by neurite degeneration and the altered distribution of axonal phosphorylated neurofilaments. |
T14 | 1446-1572 | DRI_Challenge | denotes | Importantly, the introduction of a kinase-inactive mutation (G2019S/D1994N) completely ameliorates the pathological effects of |
T15 | 1586-1683 | DRI_Challenge | denotes | in the striatum supporting a kinase activity-dependent mechanism for this PD-associated mutation. |
T16 | 1684-1917 | DRI_Outcome | denotes | Collectively, our study further elucidates the pathological effects of the G2019S mutation in the mammalian brain and supports the development of kinase inhibitors as a potential therapeutic approach for treating LRRK2-associated PD. |
T17 | 1918-2046 | DRI_Outcome | denotes | This adenoviral rodent model provides an important tool for elucidating the molecular basis of LRRK2-mediated neurodegeneration. |
DisGeNET5_variant_disease
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
25731749-0#34#40#geners34637584 | 34-40 | geners34637584 | denotes | G2019S |
25731749-0#121#140#diseaseC0030567 | 121-140 | diseaseC0030567 | denotes | Parkinson's disease |
25731749-12#75#81#geners34637584 | 1759-1765 | geners34637584 | denotes | G2019S |
25731749-12#230#232#diseaseC3489791 | 1914-1916 | diseaseC3489791 | denotes | PD |
34#40#geners34637584121#140#diseaseC0030567 | 25731749-0#34#40#geners34637584 | 25731749-0#121#140#diseaseC0030567 | associated_with | G2019S,Parkinson's disease |
75#81#geners34637584230#232#diseaseC3489791 | 25731749-12#75#81#geners34637584 | 25731749-12#230#232#diseaseC3489791 | associated_with | G2019S,PD |
DisGeNET5_gene_disease
Id | Subject | Object | Predicate | Lexical cue |
---|---|---|---|---|
25731749-0#41#46#gene120892 | 41-46 | gene120892 | denotes | LRRK2 |
25731749-0#121#140#diseaseC0030567 | 121-140 | diseaseC0030567 | denotes | Parkinson's disease |
25731749-12#213#218#gene120892 | 1897-1902 | gene120892 | denotes | LRRK2 |
25731749-12#230#232#diseaseC3489791 | 1914-1916 | diseaseC3489791 | denotes | PD |
41#46#gene120892121#140#diseaseC0030567 | 25731749-0#41#46#gene120892 | 25731749-0#121#140#diseaseC0030567 | associated_with | LRRK2,Parkinson's disease |
213#218#gene120892230#232#diseaseC3489791 | 25731749-12#213#218#gene120892 | 25731749-12#230#232#diseaseC3489791 | associated_with | LRRK2,PD |