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c_corpus

Id Subject Object Predicate Lexical cue
T5 0-19 D010300 denotes Parkinson's Disease
T6 0-19 D010300 denotes Parkinson's Disease
T9 31-36 PR:Q5S006 denotes LRRK2
T10 31-36 PR:000003033 denotes LRRK2
T11 31-36 PR:Q5S007 denotes LRRK2
T12 49-55 D010770 denotes Kinase
T13 72-88 GO:0008021 denotes Synaptic Vesicle
T14 72-100 GO:0048489 denotes Synaptic Vesicle Trafficking
T17 112-120 UBERON:0001891 denotes Midbrain
T18 142-149 D004194 denotes disease
T19 142-149 D004194 denotes disease
T20 212-228 UBERON:0002038 denotes substantia nigra
T21 306-311 PR:Q5S006 denotes LRRK2
T22 306-311 PR:000003033 denotes LRRK2
T23 306-311 PR:Q5S007 denotes LRRK2
T24 368-384 GO:0008021 denotes synaptic vesicle
T26 434-439 PR:Q5S006 denotes LRRK2
T27 434-439 PR:000003033 denotes LRRK2
T28 434-439 PR:Q5S007 denotes LRRK2
T29 537-545 SO:0000109 denotes mutation
T30 546-551 PR:Q5S006 denotes LRRK2
T31 546-551 PR:000003033 denotes LRRK2
T32 546-551 PR:Q5S007 denotes LRRK2
T33 570-581 GO:0006897 denotes endocytosis
T34 593-601 UBERON:0001891 denotes midbrain
T35 653-664 GO:0006897 denotes endocytosis
T36 697-702 PR:Q5S006 denotes LRRK2
T37 697-702 PR:000003033 denotes LRRK2
T38 697-702 PR:Q5S007 denotes LRRK2
T39 703-718 GO:0016301 denotes kinase activity
T40 777-782 PR:Q5S006 denotes LRRK2
T41 777-782 PR:000003033 denotes LRRK2
T42 777-782 PR:Q5S007 denotes LRRK2
T43 807-816 UBERON:0001950 denotes neocortex
T44 854-865 UBERON:0002421 denotes hippocampus
T45 854-865 UBERON:0001954 denotes hippocampus
T46 854-865 UBERON:0002961 denotes hippocampus
T47 880-885 UBERON:6110636 denotes brain
T48 880-885 UBERON:0000955 denotes brain
T49 930-938 SO:0000109 denotes mutation
T50 992-1003 GO:0006897 denotes endocytosis
T51 1037-1045 SO:0000159 denotes deletion
T52 1049-1054 PR:Q8CHC4 denotes SYNJ1
T53 1049-1054 PR:000015882 denotes SYNJ1
T54 1049-1054 PR:Q62910 denotes SYNJ1
T55 1049-1054 PR:O43426 denotes SYNJ1
T57 1056-1062 615530 denotes PARK20
T58 1067-1071 SO:0000704 denotes gene
T59 1106-1118 D020734 denotes Parkinsonism
T60 1106-1118 D020734 denotes Parkinsonism
T61 1130-1135 PR:Q8CHC4 denotes SYNJ1
T62 1130-1135 PR:000015882 denotes SYNJ1
T63 1130-1135 PR:Q62910 denotes SYNJ1
T64 1130-1135 PR:O43426 denotes SYNJ1
T65 1143-1148 PR:Q5S006 denotes LRRK2
T66 1143-1148 PR:000003033 denotes LRRK2
T67 1143-1148 PR:Q5S007 denotes LRRK2
T68 1179-1190 GO:0006897 denotes endocytosis
T69 1213-1223 GO:0006887 denotes exocytosis
T71 1288-1292 UBERON:0003101 denotes male
T72 1288-1292 CHEBI:30780 denotes male
T73 1293-1297 PR:000005054 denotes mice
T75 1293-1297 O89094 denotes mice
T74 1293-1297 D051379 denotes mice
T76 1293-1297 10095 denotes mice
T77 1327-1332 PR:Q5S006 denotes LRRK2
T78 1327-1332 PR:000003033 denotes LRRK2
T79 1327-1332 PR:Q5S007 denotes LRRK2
T82 1357-1370 Q62910 denotes synaptojanin1
T83 1357-1370 PR:000015882 denotes synaptojanin1
T84 1357-1370 O18964 denotes synaptojanin1
T85 1357-1370 Q8CHC4 denotes synaptojanin1
T87 1357-1370 O43426 denotes synaptojanin1
T86 1357-1370 C097702 denotes synaptojanin1
T90 1423-1436 Q62910 denotes synaptojanin1
T91 1423-1436 PR:000015882 denotes synaptojanin1
T92 1423-1436 O18964 denotes synaptojanin1
T93 1423-1436 Q8CHC4 denotes synaptojanin1
T95 1423-1436 O43426 denotes synaptojanin1
T94 1423-1436 C097702 denotes synaptojanin1
T96 1465-1476 GO:0006897 denotes endocytosis
T97 1507-1512 PR:Q5S006 denotes LRRK2
T98 1507-1512 PR:000003033 denotes LRRK2
T99 1507-1512 PR:Q5S007 denotes LRRK2
T100 1517-1522 PR:Q8CHC4 denotes SYNJ1
T101 1517-1522 PR:000015882 denotes SYNJ1
T102 1517-1522 PR:Q62910 denotes SYNJ1
T103 1517-1522 PR:O43426 denotes SYNJ1
T104 1637-1649 GO:0009405 denotes pathogenesis
T105 1687-1695 UBERON:0001891 denotes midbrain
T106 1719-1725 CL:0000540 denotes neuron
T107 1848-1853 UBERON:0001021 denotes nerve
T108 1848-1862 GO:0044306 denotes nerve terminal
T109 1957-1961 168600 denotes PARK
T110 1969-1974 PR:Q5S006 denotes LRRK2
T111 1969-1974 PR:000003033 denotes LRRK2
T112 1969-1974 PR:Q5S007 denotes LRRK2
T115 1976-1981 PR:000003033 denotes PARK8
T116 1976-1981 PR:Q5S007 denotes PARK8
T114 1976-1981 607060 denotes PARK8
T117 1987-1992 PR:Q8CHC4 denotes SYNJ1
T118 1987-1992 PR:000015882 denotes SYNJ1
T119 1987-1992 PR:Q62910 denotes SYNJ1
T120 1987-1992 PR:O43426 denotes SYNJ1
T122 1994-2000 615530 denotes PARK20
T123 2036-2051 GO:0016301 denotes kinase activity
T124 2092-2100 SO:0000109 denotes mutation
T125 2104-2109 PR:Q5S006 denotes LRRK2
T126 2104-2109 PR:000003033 denotes LRRK2
T127 2104-2109 PR:Q5S007 denotes LRRK2
T128 2177-2182 PR:Q5S006 denotes LRRK2
T129 2177-2182 PR:000003033 denotes LRRK2
T130 2177-2182 PR:Q5S007 denotes LRRK2
T131 2194-2199 PR:Q8CHC4 denotes SYNJ1
T132 2194-2199 PR:000015882 denotes SYNJ1
T133 2194-2199 PR:Q62910 denotes SYNJ1
T134 2194-2199 PR:O43426 denotes SYNJ1
T135 2244-2251 CHEBI:34922 denotes pathway
T136 2276-2282 CL:0000540 denotes neuron
T137 2286-2297 GO:0006897 denotes endocytosis

PubMed_ArguminSci

Id Subject Object Predicate Lexical cue
T1 130-265 DRI_Background denotes Parkinson's disease (PD) is characterized pathologically by the selective loss of substantia nigra (SN) dopaminergic (DAergic) neurons.
T2 266-402 DRI_Background denotes Recent evidence has suggested a role of LRRK2, linked to the most frequent familial PD, in regulating synaptic vesicle (SV) trafficking.
T3 403-499 DRI_Background denotes However, the mechanism whereby LRRK2 mutants contribute to nigral vulnerability remains unclear.
T4 500-545 DRI_Outcome denotes Here we show that the most common PD mutation
T5 559-719 DRI_Outcome denotes impairs SV endocytosis in ventral midbrain (MB) neurons, including DA neurons, and the slowed endocytosis can be rescued by inhibition of LRRK2 kinase activity.
T6 720-939 DRI_Challenge denotes A similar endocytic defect, however, was not observed in LRRK2 mutant neurons from the neocortex (hereafter, cortical neurons) or the hippocampus, suggesting a brain region-specific vulnerability to the G2019S mutation.
T7 940-1119 DRI_Approach denotes Additionally, we found MB-specific impairment of SV endocytosis in neurons carrying heterozygous deletion of SYNJ1 (PARK20), a gene that is associated with recessive Parkinsonism.
T8 1120-1142 DRI_Outcome denotes Combining SYNJ1+/- and
T9 1156-1298 DRI_Outcome denotes does not exacerbate SV endocytosis but impairs sustained exocytosis in MB neurons and alters specific motor functions of 1-year-old male mice.
T10 1299-1477 DRI_Outcome denotes Interestingly, we show that LRRK2 directly phosphorylates synaptojanin1 in vitro, resulting in the disruption of endophilin-synaptojanin1 interaction required for SV endocytosis.
T11 1478-1814 DRI_Challenge denotes Our work suggests a merge of LRRK2 and SYNJ1 pathogenic pathways in deregulating SV trafficking in MB neurons as an underlying molecular mechanism of early PD pathogenesis.SIGNIFICANCE STATEMENT Understanding midbrain dopaminergic (DAergic) neuron-selective vulnerability in PD is essential for the development of targeted therapeutics.
T12 1815-2002 DRI_Outcome denotes We report, for the first time, a nerve terminal impairment in SV trafficking selectively in MB neurons but not cortical neurons caused by two PARK genes: LRRK2 (PARK8) and SYNJ1 (PARK20).
T13 2003-2140 DRI_Outcome denotes We demonstrate that the enhanced kinase activity resulting from the most frequent G2019S mutation in LRRK2 is the key to this impairment.
T14 2141-2176 DRI_Outcome denotes We provide evidence suggesting that
T15 2190-2388 DRI_Outcome denotes and SYNJ1 loss of function share a similar pathogenic pathway in deregulating DAergic neuron SV endocytosis and that they play additive roles in facilitating each other's pathogenic functions in PD.

kaiyin_test

Id Subject Object Predicate Lexical cue
T1 0-19 Disease denotes Parkinson's Disease
T2 31-36 Gene denotes LRRK2
T3 56-62 Var denotes Mutant
T4 63-71 NegReg denotes Disrupts
T5 72-128 MPA denotes Synaptic Vesicle Trafficking in Ventral Midbrain Neurons
T6 434-439 Gene denotes LRRK2
T7 440-447 Var denotes mutants
T9 448-458 Reg denotes contribute
T8 462-482 MPA denotes nigral vulnerability
T11 537-545 Var denotes mutation
T12 546-551 Gene denotes LRRK2
T10 559-566 NegReg denotes impairs
T13 567-636 MPA denotes SV endocytosis in ventral midbrain (MB) neurons, including DA neurons
T15 975-985 NegReg denotes impairment
T16 989-1014 MPA denotes SV endocytosis in neurons
T17 1037-1045 Var denotes deletion
T14 1049-1054 Gene denotes SYNJ1
T18 1130-1138 Var denotes SYNJ1+/-
T19 1143-1155 Var denotes LRRK2 G2019S
T20 1195-1202 NegReg denotes impairs
T21 1203-1237 MPA denotes sustained exocytosis in MB neurons
T22 1242-1248 Reg denotes alters
T23 1249-1273 MPA denotes specific motor functions
T24 1327-1332 Var denotes LRRK2
T25 1381-1393 Reg denotes resulting in
T26 1398-1476 MPA denotes disruption of endophilin-synaptojanin1 interaction required for SV endocytosis
T31 2027-2035 PosReg denotes enhanced
T32 2036-2051 MPA denotes kinase activity
T28 2085-2091 Var denotes G2019S
T29 2104-2109 Gene denotes LRRK2
T39 2177-2182 Gene denotes LRRK2
T33 2183-2189 Var denotes G2019S
T34 2194-2199 Gene denotes SYNJ1
T35 2200-2216 NegReg denotes loss of function
T36 2255-2297 MPA denotes deregulating DAergic neuron SV endocytosis
T37 2312-2331 Reg denotes play additive roles
T38 2385-2387 Disease denotes PD
R1 T2 T3 ThemeOf LRRK2,Mutant
R10 T13 T10 ThemeOf "SV endocytosis in ventral midbrain (MB) neurons, including DA neurons",impairs
R11 T14 T17 ThemeOf SYNJ1,deletion
R12 T17 T15 CauseOf deletion,impairment
R13 T16 T15 ThemeOf SV endocytosis in neurons,impairment
R14 T18 T20 CauseOf SYNJ1+/-,impairs
R15 T21 T20 ThemeOf sustained exocytosis in MB neurons,impairs
R16 T19 T20 CauseOf LRRK2 G2019S,impairs
R17 T18 T22 CauseOf SYNJ1+/-,alters
R18 T19 T22 CauseOf LRRK2 G2019S,alters
R19 T23 T22 ThemeOf specific motor functions,alters
R2 T3 T4 CauseOf Mutant,Disrupts
R20 T28 T31 CauseOf G2019S,enhanced
R21 T32 T31 ThemeOf kinase activity,enhanced
R22 T29 T28 ThemeOf LRRK2,G2019S
R23 T33 T35 CauseOf G2019S,loss of function
R24 T34 T35 CauseOf SYNJ1,loss of function
R25 T36 T35 ThemeOf deregulating DAergic neuron SV endocytosis,loss of function
R26 T34 T37 CauseOf SYNJ1,play additive roles
R27 T33 T37 CauseOf G2019S,play additive roles
R28 T38 T37 ThemeOf PD,play additive roles
R29 T24 T25 CauseOf LRRK2,resulting in
R3 T5 T4 ThemeOf Synaptic Vesicle Trafficking in Ventral Midbrain Neurons,Disrupts
R30 T26 T25 ThemeOf disruption of endophilin-synaptojanin1 interaction required for SV endocytosis,resulting in
R31 T39 T33 ThemeOf LRRK2,G2019S
R4 T3 T1 CauseOf Mutant,Parkinson's Disease
R5 T6 T7 ThemeOf LRRK2,mutants
R6 T7 T9 CauseOf mutants,contribute
R7 T8 T9 ThemeOf nigral vulnerability,contribute
R8 T12 T11 ThemeOf LRRK2,mutation
R9 T11 T10 CauseOf mutation,impairs

name_no

Id Subject Object Predicate Lexical cue
T1 0-19 Disease denotes Parkinson's Disease
T2 31-36 Gene denotes LRRK2
T3 56-62 Var denotes Mutant
T4 63-71 NegReg denotes Disrupts
T5 72-128 MPA denotes Synaptic Vesicle Trafficking in Ventral Midbrain Neurons
T6 434-439 Gene denotes LRRK2
T7 440-447 Var denotes mutants
T9 448-458 Reg denotes contribute
T8 462-482 MPA denotes nigral vulnerability
T11 537-545 Var denotes mutation
T12 546-551 Gene denotes LRRK2
T10 559-566 NegReg denotes impairs
T13 567-636 MPA denotes SV endocytosis in ventral midbrain (MB) neurons, including DA neurons
T15 975-985 NegReg denotes impairment
T16 989-1014 MPA denotes SV endocytosis in neurons
T17 1037-1045 Var denotes deletion
T14 1049-1054 Gene denotes SYNJ1
T18 1130-1138 Var denotes SYNJ1+/-
T19 1143-1155 Var denotes LRRK2 G2019S
T20 1195-1202 NegReg denotes impairs
T21 1203-1237 MPA denotes sustained exocytosis in MB neurons
T22 1242-1248 Reg denotes alters
T23 1249-1273 MPA denotes specific motor functions
T24 1327-1332 Var denotes LRRK2
T25 1381-1393 Reg denotes resulting in
T26 1398-1476 MPA denotes disruption of endophilin-synaptojanin1 interaction required for SV endocytosis
T31 2027-2035 PosReg denotes enhanced
T32 2036-2051 MPA denotes kinase activity
T28 2085-2091 Var denotes G2019S
T29 2104-2109 Gene denotes LRRK2
T39 2177-2182 Gene denotes LRRK2
T33 2183-2189 Var denotes G2019S
T34 2194-2199 Gene denotes SYNJ1
T35 2200-2216 NegReg denotes loss of function
T36 2255-2297 MPA denotes deregulating DAergic neuron SV endocytosis
T37 2312-2331 Reg denotes play additive roles
T38 2385-2387 Disease denotes PD
R1 T2 T3 ThemeOf LRRK2,Mutant
R10 T13 T10 ThemeOf "SV endocytosis in ventral midbrain (MB) neurons, including DA neurons",impairs
R11 T14 T17 ThemeOf SYNJ1,deletion
R12 T17 T15 CauseOf deletion,impairment
R13 T16 T15 ThemeOf SV endocytosis in neurons,impairment
R14 T18 T20 CauseOf SYNJ1+/-,impairs
R15 T21 T20 ThemeOf sustained exocytosis in MB neurons,impairs
R16 T19 T20 CauseOf LRRK2 G2019S,impairs
R17 T18 T22 CauseOf SYNJ1+/-,alters
R18 T19 T22 CauseOf LRRK2 G2019S,alters
R19 T23 T22 ThemeOf specific motor functions,alters
R2 T3 T4 CauseOf Mutant,Disrupts
R20 T28 T31 CauseOf G2019S,enhanced
R21 T32 T31 ThemeOf kinase activity,enhanced
R22 T29 T28 ThemeOf LRRK2,G2019S
R23 T33 T35 CauseOf G2019S,loss of function
R24 T34 T35 CauseOf SYNJ1,loss of function
R25 T36 T35 ThemeOf deregulating DAergic neuron SV endocytosis,loss of function
R26 T34 T37 CauseOf SYNJ1,play additive roles
R27 T33 T37 CauseOf G2019S,play additive roles
R28 T38 T37 ThemeOf PD,play additive roles
R29 T24 T25 CauseOf LRRK2,resulting in
R3 T5 T4 ThemeOf Synaptic Vesicle Trafficking in Ventral Midbrain Neurons,Disrupts
R30 T26 T25 ThemeOf disruption of endophilin-synaptojanin1 interaction required for SV endocytosis,resulting in
R31 T39 T33 ThemeOf LRRK2,G2019S
R4 T3 T1 CauseOf Mutant,Parkinson's Disease
R5 T6 T7 ThemeOf LRRK2,mutants
R6 T7 T9 CauseOf mutants,contribute
R7 T8 T9 ThemeOf nigral vulnerability,contribute
R8 T12 T11 ThemeOf LRRK2,mutation
R9 T11 T10 CauseOf mutation,impairs