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PubMed:26251043 JSONTXT

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c_corpus

Id Subject Object Predicate Lexical cue
T1 11-16 PR:Q5S006 denotes LRRK2
T2 11-16 PR:000003033 denotes LRRK2
T3 11-16 PR:Q5S007 denotes LRRK2
T4 46-61 GO:0016301 denotes kinase activity
T6 137-140 318 denotes ATP
T5 137-140 D000255 denotes ATP
T7 137-140 CHEBI:30616 denotes ATP
T8 137-140 D000255 denotes ATP
T9 137-140 CHEBI:15422 denotes ATP
T15 137-144 PR:000031171 denotes ATP13A2
T16 137-144 PR:Q9NQ11 denotes ATP13A2
T17 137-144 PR:Q9CTG6 denotes ATP13A2
T18 207-219 GO:0009405 denotes pathogenesis
T21 231-258 D019636 denotes neurodegenerative disorders
T22 231-258 D019636 denotes neurodegenerative disorders
T27 270-289 D010300 denotes Parkinson's disease
T28 270-289 D010300 denotes Parkinson's disease
T32 351-358 6308 denotes leucine
T33 351-358 SO:0001437 denotes leucine
T31 351-358 CHEBI:15603 denotes leucine
T34 351-358 D007930 denotes leucine
T35 351-358 CHEBI:25017 denotes leucine
T36 351-358 D007930 denotes leucine
T37 364-370 SO:0001068 denotes repeat
T38 381-386 PR:Q5S006 denotes LRRK2
T39 381-386 PR:000003033 denotes LRRK2
T40 381-386 PR:Q5S007 denotes LRRK2
T41 455-460 PR:Q5S006 denotes LRRK2
T42 455-460 PR:000003033 denotes LRRK2
T43 455-460 PR:Q5S007 denotes LRRK2
T44 490-508 C566739 denotes autosomal-dominant
T45 625-630 PR:Q5S006 denotes LRRK2
T46 625-630 PR:000003033 denotes LRRK2
T47 625-630 PR:Q5S007 denotes LRRK2
T48 641-649 GO:0005764 denotes lysosome
T49 733-738 PR:Q5S006 denotes LRRK2
T50 733-738 PR:000003033 denotes LRRK2
T51 733-738 PR:Q5S007 denotes LRRK2
T52 754-759 PR:Q5S006 denotes LRRK2
T53 754-759 PR:000003033 denotes LRRK2
T54 754-759 PR:Q5S007 denotes LRRK2
T55 797-805 SO:0000109 denotes mutation
T56 968-973 PR:Q5S006 denotes LRRK2
T57 968-973 PR:000003033 denotes LRRK2
T58 968-973 PR:Q5S007 denotes LRRK2
T59 1043-1048 PR:Q5S006 denotes LRRK2
T60 1043-1048 PR:000003033 denotes LRRK2
T61 1043-1048 PR:Q5S007 denotes LRRK2
T62 1158-1176 GO:0003824 denotes catalytic activity
T63 1218-1223 PR:Q5S006 denotes LRRK2
T64 1218-1223 PR:000003033 denotes LRRK2
T65 1218-1223 PR:Q5S007 denotes LRRK2
T68 1227-1233 9671 denotes serine
T70 1227-1233 SO:0001444 denotes serine
T66 1227-1233 D012694 denotes serine
T67 1227-1233 CHEBI:17822 denotes serine
T69 1227-1233 D012694 denotes serine
T71 1227-1233 CHEBI:17115 denotes serine
T72 1278-1283 PR:Q5S006 denotes LRRK2
T73 1278-1283 PR:000003033 denotes LRRK2
T74 1278-1283 PR:Q5S007 denotes LRRK2
T75 1286-1301 GO:0016301 denotes kinase activity
T76 1333-1342 CHEBI:35222 denotes inhibitor
T77 1343-1354 C000597233 denotes PF-06447475
T78 1343-1354 C000597233 denotes PF-06447475
T79 1470-1478 SO:0000109 denotes mutation
T81 1490-1499 MOP:0000569 denotes reduction
T82 1558-1564 A3DIJ8 denotes ATPase
T84 1558-1564 Q9SIY3 denotes ATPase
T83 1558-1564 D000251 denotes ATPase
T86 1565-1568 318 denotes ATP
T85 1565-1568 D000255 denotes ATP
T87 1565-1568 CHEBI:30616 denotes ATP
T88 1565-1568 D000255 denotes ATP
T89 1565-1568 CHEBI:15422 denotes ATP
T95 1565-1572 PR:000031171 denotes ATP13A2
T96 1565-1572 PR:Q9NQ11 denotes ATP13A2
T97 1565-1572 PR:Q9CTG6 denotes ATP13A2
T98 1576-1580 SO:0000704 denotes gene
T100 1593-1614 D020734 denotes parkinsonian syndrome
T101 1593-1614 D020734 denotes parkinsonian syndrome
T102 1616-1636 C537177 denotes Kufor-Rakeb syndrome
T103 1616-1636 C537177 denotes Kufor-Rakeb syndrome
T104 1642-1647 UBERON:6110636 denotes brain
T105 1642-1647 UBERON:0000955 denotes brain
T106 1661-1666 10090 denotes mouse
T107 1661-1666 D051379 denotes mouse
T108 1671-1676 D006801 denotes human
T109 1677-1682 PR:Q5S006 denotes LRRK2
T110 1677-1682 PR:000003033 denotes LRRK2
T111 1677-1682 PR:Q5S007 denotes LRRK2
T112 1690-1698 CHEBI:78059 denotes carriers
T113 1755-1760 PR:Q5S006 denotes LRRK2
T114 1755-1760 PR:000003033 denotes LRRK2
T115 1755-1760 PR:Q5S007 denotes LRRK2
T116 1779-1787 GO:0005764 denotes lysosome
T117 1867-1872 PR:Q5S006 denotes LRRK2
T118 1867-1872 PR:000003033 denotes LRRK2
T119 1867-1872 PR:Q5S007 denotes LRRK2
T120 1880-1890 CHEBI:35222 denotes inhibitors

PubMed_ArguminSci

Id Subject Object Predicate Lexical cue
T1 157-295 DRI_Challenge denotes Lysosomal dysfunction plays a central role in the pathogenesis of several neurodegenerative disorders, including Parkinson's disease (PD).
T2 296-435 DRI_Background denotes Several genes linked to genetic forms of PD, including leucine-rich repeat kinase 2 (LRRK2), functionally converge on the lysosomal system.
T3 436-598 DRI_Background denotes While mutations in LRRK2 are commonly associated with autosomal-dominant PD, the physiological and pathological functions of this kinase remain poorly understood.
T4 599-739 DRI_Outcome denotes Here, we demonstrate that LRRK2 regulates lysosome size, number and function in astrocytes, which endogenously express high levels of LRRK2.
T5 740-753 DRI_Challenge denotes Expression of
T6 766-888 DRI_Challenge denotes , the most common pathological mutation, produces enlarged lysosomes and diminishes the lysosomal capacity of these cells.
T7 889-1077 DRI_Background denotes Enlarged lysosomes appears to be a common phenotype associated with pathogenic LRRK2 mutations, as we also observed this effect in cells expressing other LRRK2 mutations; R1441C or Y1699C.
T8 1078-1239 DRI_Challenge denotes The lysosomal defects associated with these mutations are dependent on both the catalytic activity of the kinase and autophosphorylation of LRRK2 at serine 1292.
T9 1240-1422 DRI_Outcome denotes Further, we demonstrate that blocking LRRK2's kinase activity, with the potent and selective inhibitor PF-06447475, rescues the observed defects in lysosomal morphology and function.
T10 1423-1676 DRI_Challenge denotes The present study also establishes that G2019S mutation leads to a reduction in lysosomal pH and increased expression of the lysosomal ATPase ATP13A2, a gene linked to a parkinsonian syndrome (Kufor-Rakeb syndrome), in brain samples from mouse and human
T11 1690-1699 DRI_Challenge denotes carriers.
T12 1700-1740 DRI_Outcome denotes Together, these results demonstrate that
T13 1761-1914 DRI_Outcome denotes mutations perturb lysosome function in a kinase-dependent manner, highlighting the therapeutic promise of LRRK2 kinase inhibitors in the treatment of PD.

DisGeNET5_variant_disease

Id Subject Object Predicate Lexical cue
26251043-9#260#266#geners34637584 1683-1689 geners34637584 denotes G2019S
26251043-9#40#46#geners34637584 1463-1469 geners34637584 denotes G2019S
26251043-9#170#191#diseaseC0242422 1593-1614 diseaseC0242422 denotes parkinsonian syndrome
26251043-9#193#213#diseaseC1847640 1616-1636 diseaseC1847640 denotes Kufor-Rakeb syndrome
260#266#geners34637584170#191#diseaseC0242422 26251043-9#260#266#geners34637584 26251043-9#170#191#diseaseC0242422 associated_with G2019S,parkinsonian syndrome
260#266#geners34637584193#213#diseaseC1847640 26251043-9#260#266#geners34637584 26251043-9#193#213#diseaseC1847640 associated_with G2019S,Kufor-Rakeb syndrome
40#46#geners34637584170#191#diseaseC0242422 26251043-9#40#46#geners34637584 26251043-9#170#191#diseaseC0242422 associated_with G2019S,parkinsonian syndrome
40#46#geners34637584193#213#diseaseC1847640 26251043-9#40#46#geners34637584 26251043-9#193#213#diseaseC1847640 associated_with G2019S,Kufor-Rakeb syndrome

DisGeNET5_gene_disease

Id Subject Object Predicate Lexical cue
26251043-10#55#60#gene120892 1755-1760 gene120892 denotes LRRK2
26251043-10#167#172#gene120892 1867-1872 gene120892 denotes LRRK2
26251043-10#41#43#diseaseC0030567 1741-1743 diseaseC0030567 denotes PD
26251043-10#211#213#diseaseC0030567 1911-1913 diseaseC0030567 denotes PD
26251043-10#41#43#diseaseC0030567 1741-1743 diseaseC0030567 denotes PD
26251043-10#211#213#diseaseC0030567 1911-1913 diseaseC0030567 denotes PD
26251043-9#135#141#gene1769 1558-1564 gene1769 denotes ATPase
26251043-9#142#149#gene23400 1565-1572 gene23400 denotes ATP13A2
26251043-9#254#259#gene120892 1677-1682 gene120892 denotes LRRK2
26251043-9#170#191#diseaseC0242422 1593-1614 diseaseC0242422 denotes parkinsonian syndrome
26251043-9#193#213#diseaseC1847640 1616-1636 diseaseC1847640 denotes Kufor-Rakeb syndrome
26251043-9#170#191#diseaseC0242422 1593-1614 diseaseC0242422 denotes parkinsonian syndrome
26251043-9#193#213#diseaseC1847640 1616-1636 diseaseC1847640 denotes Kufor-Rakeb syndrome
55#60#gene12089241#43#diseaseC0030567 26251043-10#55#60#gene120892 26251043-10#41#43#diseaseC0030567 associated_with LRRK2,PD
55#60#gene120892211#213#diseaseC0030567 26251043-10#55#60#gene120892 26251043-10#211#213#diseaseC0030567 associated_with LRRK2,PD
55#60#gene12089241#43#diseaseC0030567 26251043-10#55#60#gene120892 26251043-10#41#43#diseaseC0030567 associated_with LRRK2,PD
55#60#gene120892211#213#diseaseC0030567 26251043-10#55#60#gene120892 26251043-10#211#213#diseaseC0030567 associated_with LRRK2,PD
167#172#gene12089241#43#diseaseC0030567 26251043-10#167#172#gene120892 26251043-10#41#43#diseaseC0030567 associated_with LRRK2,PD
167#172#gene120892211#213#diseaseC0030567 26251043-10#167#172#gene120892 26251043-10#211#213#diseaseC0030567 associated_with LRRK2,PD
167#172#gene12089241#43#diseaseC0030567 26251043-10#167#172#gene120892 26251043-10#41#43#diseaseC0030567 associated_with LRRK2,PD
167#172#gene120892211#213#diseaseC0030567 26251043-10#167#172#gene120892 26251043-10#211#213#diseaseC0030567 associated_with LRRK2,PD
135#141#gene1769170#191#diseaseC0242422 26251043-9#135#141#gene1769 26251043-9#170#191#diseaseC0242422 associated_with ATPase,parkinsonian syndrome
135#141#gene1769193#213#diseaseC1847640 26251043-9#135#141#gene1769 26251043-9#193#213#diseaseC1847640 associated_with ATPase,Kufor-Rakeb syndrome
135#141#gene1769170#191#diseaseC0242422 26251043-9#135#141#gene1769 26251043-9#170#191#diseaseC0242422 associated_with ATPase,parkinsonian syndrome
135#141#gene1769193#213#diseaseC1847640 26251043-9#135#141#gene1769 26251043-9#193#213#diseaseC1847640 associated_with ATPase,Kufor-Rakeb syndrome
142#149#gene23400170#191#diseaseC0242422 26251043-9#142#149#gene23400 26251043-9#170#191#diseaseC0242422 associated_with ATP13A2,parkinsonian syndrome
142#149#gene23400193#213#diseaseC1847640 26251043-9#142#149#gene23400 26251043-9#193#213#diseaseC1847640 associated_with ATP13A2,Kufor-Rakeb syndrome
142#149#gene23400170#191#diseaseC0242422 26251043-9#142#149#gene23400 26251043-9#170#191#diseaseC0242422 associated_with ATP13A2,parkinsonian syndrome
142#149#gene23400193#213#diseaseC1847640 26251043-9#142#149#gene23400 26251043-9#193#213#diseaseC1847640 associated_with ATP13A2,Kufor-Rakeb syndrome
254#259#gene120892170#191#diseaseC0242422 26251043-9#254#259#gene120892 26251043-9#170#191#diseaseC0242422 associated_with LRRK2,parkinsonian syndrome
254#259#gene120892193#213#diseaseC1847640 26251043-9#254#259#gene120892 26251043-9#193#213#diseaseC1847640 associated_with LRRK2,Kufor-Rakeb syndrome
254#259#gene120892170#191#diseaseC0242422 26251043-9#254#259#gene120892 26251043-9#170#191#diseaseC0242422 associated_with LRRK2,parkinsonian syndrome
254#259#gene120892193#213#diseaseC1847640 26251043-9#254#259#gene120892 26251043-9#193#213#diseaseC1847640 associated_with LRRK2,Kufor-Rakeb syndrome