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PubMed:29038245 JSONTXT

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PubTator4TogoVar

Id Subject Object Predicate Lexical cue proteinmutation
29038245_0 841-847 ProteinMutation denotes G2019S rs34637584
29038245_1 853-859 ProteinMutation denotes R1441C rs33939927

c_corpus

Id Subject Object Predicate Lexical cue
T3 14-21 1895 denotes Calcium
T1 14-21 D002118 denotes Calcium
T2 14-21 CHEBI:22984 denotes Calcium
T4 14-21 D002118 denotes Calcium
T5 51-59 GO:0030425 denotes Dendrite
T6 88-91 D020192 denotes LBD
T7 103-108 PR:Q5S006 denotes LRRK2
T8 103-108 PR:000003033 denotes LRRK2
T9 103-108 PR:Q5S007 denotes LRRK2
T11 131-138 6308 denotes leucine
T12 131-138 SO:0001437 denotes leucine
T10 131-138 CHEBI:15603 denotes leucine
T13 131-138 D007930 denotes leucine
T14 131-138 CHEBI:25017 denotes leucine
T15 131-138 D007930 denotes leucine
T16 144-150 SO:0001068 denotes repeat
T17 161-166 PR:Q5S006 denotes LRRK2
T18 161-166 PR:000003033 denotes LRRK2
T19 161-166 PR:Q5S007 denotes LRRK2
T20 197-207 D000067562 denotes late-onset
T21 197-207 D000067562 denotes late-onset
T26 217-236 D010300 denotes Parkinson's disease
T27 217-236 D010300 denotes Parkinson's disease
T30 279-300 D060825 denotes cognitive dysfunction
T33 337-344 1895 denotes Calcium
T31 337-344 D002118 denotes Calcium
T32 337-344 CHEBI:22984 denotes Calcium
T34 337-344 D002118 denotes Calcium
T35 389-401 GO:0009405 denotes pathogenesis
T36 503-520 GO:0007268 denotes neurotransmission
T37 559-564 PR:Q5S006 denotes LRRK2
T38 559-564 PR:000003033 denotes LRRK2
T39 559-564 PR:Q5S007 denotes LRRK2
T40 647-659 GO:0005739 denotes mitochondria
T41 714-721 1895 denotes calcium
T42 714-721 CHEBI:29320 denotes calcium
T43 714-721 CHEBI:22984 denotes calcium
T44 766-773 1895 denotes calcium
T45 766-773 CHEBI:29320 denotes calcium
T46 766-773 CHEBI:22984 denotes calcium
T47 835-840 PR:Q5S006 denotes LRRK2
T48 835-840 PR:000003033 denotes LRRK2
T49 835-840 PR:Q5S007 denotes LRRK2
T50 882-887 10090 denotes mouse
T51 882-887 D051379 denotes mouse
T52 951-979 GO:0036444 denotes mitochondrial calcium uptake
T53 965-972 1895 denotes calcium
T54 965-972 CHEBI:29320 denotes calcium
T55 965-972 CHEBI:22984 denotes calcium
T58 1016-1021 PR:Q5S006 denotes LRRK2
T59 1016-1021 PR:000003033 denotes LRRK2
T60 1016-1021 PR:Q5S007 denotes LRRK2
T62 1067-1098 Q9SZ45 denotes mitochondrial calcium uniporter
T63 1067-1098 Q8IQ70 denotes mitochondrial calcium uniporter
T61 1067-1098 C034703 denotes mitochondrial calcium uniporter
T64 1081-1088 1895 denotes calcium
T68 1100-1103 PR:Q08BI9 denotes MCU
T69 1100-1103 PR:000032782 denotes MCU
T70 1100-1103 PR:Q8IQ70 denotes MCU
T71 1100-1103 PR:Q8NE86 denotes MCU
T72 1100-1103 PR:Q3UMR5 denotes MCU
T73 1113-1141 GO:0036444 denotes mitochondrial calcium uptake
T74 1113-1143 A2VEI2 denotes mitochondrial calcium uptake 1
T75 1127-1134 1895 denotes calcium
T76 1127-1134 CHEBI:29320 denotes calcium
T77 1127-1134 CHEBI:22984 denotes calcium
T84 1144-1151 SO:0000104 denotes protein
T83 1144-1151 PR:000000001 denotes protein
T81 1144-1151 CHEBI:36080 denotes protein
T82 1144-1151 CHEBI:11122 denotes protein
T80 1144-1151 GO:0003675 denotes protein
T86 1153-1158 PR:Q9BPX6 denotes MICU1
T87 1153-1158 PR:Q8VCX5 denotes MICU1
T88 1153-1158 PR:Q6P6Q9 denotes MICU1
T89 1153-1158 PR:A4IG32 denotes MICU1
T90 1153-1158 PR:A2VEI2 denotes MICU1
T91 1153-1158 PR:Q95PZ2 denotes MICU1
T92 1153-1158 PR:000005066 denotes MICU1
T93 1206-1213 1895 denotes calcium
T94 1206-1213 CHEBI:29320 denotes calcium
T95 1206-1213 CHEBI:22984 denotes calcium
T96 1225-1229 PR:000015003 denotes NCLX
T97 1225-1229 PR:Q6J4K2 denotes NCLX
T98 1225-1229 PR:Q925Q3 denotes NCLX
T99 1225-1229 PR:Q6AXS0 denotes NCLX
T100 1240-1243 PR:Q08BI9 denotes MCU
T101 1240-1243 PR:000032782 denotes MCU
T102 1240-1243 PR:Q8IQ70 denotes MCU
T103 1240-1243 PR:Q8NE86 denotes MCU
T104 1240-1243 PR:Q3UMR5 denotes MCU
T106 1248-1253 PR:Q9BPX6 denotes MICU1
T107 1248-1253 PR:Q8VCX5 denotes MICU1
T108 1248-1253 PR:Q6P6Q9 denotes MICU1
T109 1248-1253 PR:A4IG32 denotes MICU1
T110 1248-1253 PR:A2VEI2 denotes MICU1
T111 1248-1253 PR:Q95PZ2 denotes MICU1
T112 1248-1253 PR:000005066 denotes MICU1
T113 1276-1281 PR:Q5S006 denotes LRRK2
T114 1276-1281 PR:000003033 denotes LRRK2
T115 1276-1281 PR:Q5S007 denotes LRRK2
T116 1332-1360 GO:0036444 denotes mitochondrial calcium uptake
T117 1346-1353 1895 denotes calcium
T118 1346-1353 CHEBI:29320 denotes calcium
T119 1346-1353 CHEBI:22984 denotes calcium
T122 1402-1405 D003966 denotes PDD
T123 1462-1465 PR:Q08BI9 denotes MCU
T124 1462-1465 PR:000032782 denotes MCU
T125 1462-1465 PR:Q8IQ70 denotes MCU
T126 1462-1465 PR:Q8NE86 denotes MCU
T127 1462-1465 PR:Q3UMR5 denotes MCU
T129 1470-1475 PR:Q9BPX6 denotes MICU1
T130 1470-1475 PR:Q8VCX5 denotes MICU1
T131 1470-1475 PR:Q6P6Q9 denotes MICU1
T132 1470-1475 PR:A4IG32 denotes MICU1
T133 1470-1475 PR:A2VEI2 denotes MICU1
T134 1470-1475 PR:Q95PZ2 denotes MICU1
T135 1470-1475 PR:000005066 denotes MICU1
T139 1508-1512 Q63844 denotes ERK1
T140 1508-1512 P27361 denotes ERK1
T141 1508-1512 P21708 denotes ERK1
T142 1508-1512 PR:000000104 denotes ERK1
T143 1508-1512 PR:P42525 denotes ERK1
T144 1508-1512 Q5A1D3 denotes ERK1
T145 1508-1512 P42525 denotes ERK1
T146 1508-1512 PR:P27361 denotes ERK1
T147 1508-1512 PR:P21708 denotes ERK1
T149 1508-1512 PR:Q63844 denotes ERK1
T150 1508-1512 C4YGK0 denotes ERK1
T151 1508-1512 PR:Q5A1D3 denotes ERK1
T148 1508-1512 GO:0004707 denotes ERK1
T156 1516-1520 GO:0004707 denotes MAPK
T159 1516-1521 Q63844 denotes MAPK3
T160 1516-1521 P27361 denotes MAPK3
T161 1516-1521 P21708 denotes MAPK3
T162 1516-1521 PR:000000104 denotes MAPK3
T163 1516-1521 PR:P27361 denotes MAPK3
T164 1516-1521 PR:P21708 denotes MAPK3
T165 1516-1521 PR:Q63844 denotes MAPK3
T166 1516-1521 PR:000028876 denotes MAPK3
T167 1525-1532 CHEBI:34922 denotes pathway
T171 1545-1549 Q63844 denotes ERK1
T172 1545-1549 P27361 denotes ERK1
T173 1545-1549 P21708 denotes ERK1
T174 1545-1549 PR:000000104 denotes ERK1
T175 1545-1549 PR:P42525 denotes ERK1
T176 1545-1549 Q5A1D3 denotes ERK1
T177 1545-1549 P42525 denotes ERK1
T178 1545-1549 PR:P27361 denotes ERK1
T179 1545-1549 PR:P21708 denotes ERK1
T181 1545-1549 PR:Q63844 denotes ERK1
T182 1545-1549 C4YGK0 denotes ERK1
T183 1545-1549 PR:Q5A1D3 denotes ERK1
T180 1545-1549 GO:0004707 denotes ERK1
T184 1588-1593 PR:Q5S006 denotes LRRK2
T185 1588-1593 PR:000003033 denotes LRRK2
T186 1588-1593 PR:Q5S007 denotes LRRK2
T187 1602-1609 GO:0043005 denotes neurite
T188 1638-1648 CHEBI:35222 denotes inhibitors
T189 1652-1656 GO:0016246 denotes RNAi
T190 1670-1673 PR:Q08BI9 denotes MCU
T191 1670-1673 PR:000032782 denotes MCU
T192 1670-1673 PR:Q8IQ70 denotes MCU
T193 1670-1673 PR:Q8NE86 denotes MCU
T194 1670-1673 PR:Q3UMR5 denotes MCU
T195 1685-1713 GO:0036444 denotes mitochondrial calcium uptake
T196 1699-1706 1895 denotes calcium
T197 1699-1706 CHEBI:29320 denotes calcium
T198 1699-1706 CHEBI:22984 denotes calcium
T201 1767-1772 PR:Q5S006 denotes LRRK2
T202 1767-1772 PR:000003033 denotes LRRK2
T203 1767-1772 PR:Q5S007 denotes LRRK2
T204 1830-1834 PR:000015003 denotes NCLX
T205 1830-1834 PR:Q6J4K2 denotes NCLX
T206 1830-1834 PR:Q925Q3 denotes NCLX
T207 1830-1834 PR:Q6AXS0 denotes NCLX
T208 1849-1856 1895 denotes calcium
T209 1849-1856 CHEBI:29320 denotes calcium
T210 1849-1856 CHEBI:22984 denotes calcium
T211 1869-1881 GO:0005739 denotes mitochondria
T212 1940-1954 D004198 denotes susceptibility
T213 1940-1954 D004198 denotes susceptibility
T214 1972-1979 1895 denotes calcium
T215 1972-1979 CHEBI:29320 denotes calcium
T216 1972-1979 CHEBI:22984 denotes calcium
T217 2036-2041 PR:Q5S006 denotes LRRK2
T218 2036-2041 PR:000003033 denotes LRRK2
T219 2036-2041 PR:Q5S007 denotes LRRK2
T220 2042-2054 GO:0009405 denotes pathogenesis
T221 2078-2099 D060825 denotes Cognitive dysfunction
T222 2104-2112 D003704 denotes dementia
T223 2104-2112 D003704 denotes dementia
T228 2136-2155 D010300 denotes Parkinson's disease
T229 2136-2155 D010300 denotes Parkinson's disease
T232 2207-2212 PR:Q5S006 denotes LRRK2
T233 2207-2212 PR:000003033 denotes LRRK2
T234 2207-2212 PR:Q5S007 denotes LRRK2
T235 2290-2295 PR:Q5S006 denotes LRRK2
T236 2290-2295 PR:000003033 denotes LRRK2
T237 2290-2295 PR:Q5S007 denotes LRRK2
T238 2330-2358 GO:0036444 denotes mitochondrial calcium uptake
T239 2344-2351 1895 denotes calcium
T240 2344-2351 CHEBI:29320 denotes calcium
T241 2344-2351 CHEBI:22984 denotes calcium
T244 2473-2480 1895 denotes calcium
T245 2473-2480 CHEBI:29320 denotes calcium
T246 2473-2480 CHEBI:22984 denotes calcium
T247 2493-2496 PR:Q08BI9 denotes MCU
T248 2493-2496 PR:000032782 denotes MCU
T249 2493-2496 PR:Q8IQ70 denotes MCU
T250 2493-2496 PR:Q8NE86 denotes MCU
T251 2493-2496 PR:Q3UMR5 denotes MCU
T255 2511-2515 Q63844 denotes ERK1
T256 2511-2515 P27361 denotes ERK1
T257 2511-2515 P21708 denotes ERK1
T258 2511-2515 PR:000000104 denotes ERK1
T259 2511-2515 PR:P42525 denotes ERK1
T260 2511-2515 Q5A1D3 denotes ERK1
T261 2511-2515 P42525 denotes ERK1
T262 2511-2515 PR:P27361 denotes ERK1
T263 2511-2515 PR:P21708 denotes ERK1
T265 2511-2515 PR:Q63844 denotes ERK1
T266 2511-2515 C4YGK0 denotes ERK1
T267 2511-2515 PR:Q5A1D3 denotes ERK1
T264 2511-2515 GO:0004707 denotes ERK1
T268 2544-2547 PR:Q08BI9 denotes MCU
T269 2544-2547 PR:000032782 denotes MCU
T270 2544-2547 PR:Q8IQ70 denotes MCU
T271 2544-2547 PR:Q8NE86 denotes MCU
T272 2544-2547 PR:Q3UMR5 denotes MCU
T273 2584-2589 PR:Q5S006 denotes LRRK2
T274 2584-2589 PR:000003033 denotes LRRK2
T275 2584-2589 PR:Q5S007 denotes LRRK2
T276 2599-2607 GO:0030425 denotes dendrite
T277 2638-2641 PR:Q08BI9 denotes MCU
T278 2638-2641 PR:000032782 denotes MCU
T279 2638-2641 PR:Q8IQ70 denotes MCU
T280 2638-2641 PR:Q8NE86 denotes MCU
T281 2638-2641 PR:Q3UMR5 denotes MCU
T282 2651-2658 1895 denotes calcium
T283 2651-2658 CHEBI:29320 denotes calcium
T284 2651-2658 CHEBI:22984 denotes calcium
T285 2705-2712 1895 denotes calcium
T286 2705-2712 CHEBI:29320 denotes calcium
T287 2705-2712 CHEBI:22984 denotes calcium
T288 2718-2730 GO:0005739 denotes mitochondria
T289 2791-2805 D004198 denotes susceptibility
T290 2791-2805 D004198 denotes susceptibility
T291 2823-2830 1895 denotes calcium
T292 2823-2830 CHEBI:29320 denotes calcium
T293 2823-2830 CHEBI:22984 denotes calcium
T294 2843-2848 PR:Q5S006 denotes LRRK2
T295 2843-2848 PR:000003033 denotes LRRK2
T296 2843-2848 PR:Q5S007 denotes LRRK2
T297 2943-2964 D060825 denotes cognitive dysfunction

PubMed_ArguminSci

Id Subject Object Predicate Lexical cue
T1 118-336 DRI_Outcome denotes Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to development of late-onset familial Parkinson's disease (PD), with clinical features of motor and cognitive dysfunction indistinguishable from sporadic PD.
T2 337-458 DRI_Challenge denotes Calcium dysregulation plays an important role in PD pathogenesis, but the mechanisms of neurodegeneration remain unclear.
T3 459-643 DRI_Background denotes Recent reports indicate enhanced excitatory neurotransmission in cortical neurons expressing mutant LRRK2, which occurs before the well-characterized phenotype of dendritic shortening.
T4 644-870 DRI_Background denotes As mitochondria play a major role in the rapid buffering of cytosolic calcium, we hypothesized that altered mitochondrial calcium handling contributes to dendritic retraction elicited by the LRRK2-G2019S and -R1441C mutations.
T5 871-980 DRI_Outcome denotes In primary mouse cortical neurons, we observed increased depolarization-induced mitochondrial calcium uptake.
T6 981-1230 DRI_Outcome denotes We found that expression of mutant LRRK2 elicited transcriptional upregulation of the mitochondrial calcium uniporter (MCU) and the mitochondrial calcium uptake 1 protein (MICU1) with no change in levels of the mitochondrial calcium antiporter NCLX.
T7 1231-1429 DRI_Background denotes Elevated MCU and MICU1 were also observed in LRRK2-mutated patient fibroblasts, along with increased mitochondrial calcium uptake, and in postmortem brains of sporadic PD/PDD patients of both sexes.
T8 1430-1533 DRI_Background denotes Transcriptional upregulation of MCU and MICU1 was caused by activation of the ERK1/2 (MAPK3/1) pathway.
T9 1534-1621 DRI_Background denotes Inhibiting ERK1/2 conferred protection against mutant LRRK2-induced neurite shortening.
T10 1622-1902 DRI_Background denotes Pharmacological inhibitors or RNAi knockdown of MCU attenuated mitochondrial calcium uptake and dendritic/neuritic shortening elicited by mutant LRRK2, whereas expression of a constitutively active mutant of NCLX that enhances calcium export from mitochondria was neuroprotective.
T11 1903-2035 DRI_Challenge denotes These data suggest that an increased susceptibility to mitochondrial calcium dysregulation contributes to dendritic injury in mutant
T12 2068-2193 DRI_Challenge denotes STATEMENT Cognitive dysfunction and dementia are common features of Parkinson's disease (PD), causing significant disability.
T13 2194-2265 DRI_Background denotes Mutations in LRRK2 represent the most common known genetic cause of PD.
T14 2266-2279 DRI_Outcome denotes We found that
T15 2296-2497 DRI_Outcome denotes mutations increased dendritic and mitochondrial calcium uptake in cortical neurons and familial PD patient fibroblasts, accompanied by increased expression of the mitochondrial calcium transporter MCU.
T16 2498-2666 DRI_Background denotes Blocking the ERK1/2-dependent upregulation of MCU conferred protection against mutant LRRK2-elicited dendrite shortening, as did inhibiting MCU-mediated calcium import.
T17 2667-2756 DRI_Background denotes Conversely, stimulating the export of calcium from mitochondria was also neuroprotective.
T18 2757-2971 DRI_Challenge denotes These results implicate increased susceptibility to mitochondrial calcium overload in LRRK2-driven neurodegeneration, and suggest possible interventions that may slow the progression of cognitive dysfunction in PD.