PubMed:21362567 JSONTXT

Annnotations TAB JSON ListView MergeView

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/21362567","sourcedb":"PubMed","sourceid":"21362567","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/21362567","text":"LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress.\nStudies of Parkinson's disease (PD) have been hindered by lack of access to affected human dopaminergic (DA) neurons. Here, we report generation of induced pluripotent stem cells that carry the p.G2019S mutation (G2019S-iPSCs) in the Leucine-Rich Repeat Kinase-2 (LRRK2) gene, the most common PD-related mutation, and their differentiation into DA neurons. The high penetrance of the LRRK2 mutation and its clinical resemblance to sporadic PD suggest that these cells could provide a valuable platform for disease analysis and drug development. We found that DA neurons derived from G2019S-iPSCs showed increased expression of key oxidative stress-response genes and α-synuclein protein. The mutant neurons were also more sensitive to caspase-3 activation and cell death caused by exposure to stress agents, such as hydrogen peroxide, MG-132, and 6-hydroxydopamine, than control DA neurons. This enhanced stress sensitivity is consistent with existing understanding of early PD phenotypes and represents a potential therapeutic target.","tracks":[{"project":"Allie","denotations":[{"id":"SS1_21362567_1_0","span":{"begin":106,"end":125},"obj":"expanded"},{"id":"SS2_21362567_1_0","span":{"begin":127,"end":129},"obj":"abbr"},{"id":"SS1_21362567_1_1","span":{"begin":186,"end":198},"obj":"expanded"},{"id":"SS2_21362567_1_1","span":{"begin":200,"end":202},"obj":"abbr"},{"id":"SS1_21362567_2_0","span":{"begin":329,"end":357},"obj":"expanded"},{"id":"SS2_21362567_2_0","span":{"begin":359,"end":364},"obj":"abbr"}],"relations":[{"id":"AE1_21362567_1_0","pred":"abbreviatedTo","subj":"SS1_21362567_1_0","obj":"SS2_21362567_1_0"},{"id":"AE1_21362567_1_1","pred":"abbreviatedTo","subj":"SS1_21362567_1_1","obj":"SS2_21362567_1_1"},{"id":"AE1_21362567_2_0","pred":"abbreviatedTo","subj":"SS1_21362567_2_0","obj":"SS2_21362567_2_0"}],"attributes":[{"subj":"SS1_21362567_1_0","pred":"source","obj":"Allie"},{"subj":"SS2_21362567_1_0","pred":"source","obj":"Allie"},{"subj":"SS1_21362567_1_1","pred":"source","obj":"Allie"},{"subj":"SS2_21362567_1_1","pred":"source","obj":"Allie"},{"subj":"SS1_21362567_2_0","pred":"source","obj":"Allie"},{"subj":"SS2_21362567_2_0","pred":"source","obj":"Allie"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":106,"end":115},"obj":"HP_0001300"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":0,"end":5},"obj":"gene:120892"},{"id":"T1","span":{"begin":87,"end":93},"obj":"disease:C3825627"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_variant_disease","denotations":[{"id":"21362567-2#95#101#geners34637584","span":{"begin":308,"end":314},"obj":"geners34637584"},{"id":"21362567-2#76#84#geners34637584","span":{"begin":289,"end":297},"obj":"geners34637584"},{"id":"21362567-2#175#177#diseaseC0030567","span":{"begin":388,"end":390},"obj":"diseaseC0030567"}],"relations":[{"id":"95#101#geners34637584175#177#diseaseC0030567","pred":"associated_with","subj":"21362567-2#95#101#geners34637584","obj":"21362567-2#175#177#diseaseC0030567"},{"id":"76#84#geners34637584175#177#diseaseC0030567","pred":"associated_with","subj":"21362567-2#76#84#geners34637584","obj":"21362567-2#175#177#diseaseC0030567"}],"attributes":[{"subj":"21362567-2#95#101#geners34637584","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"21362567-2#76#84#geners34637584","pred":"source","obj":"DisGeNET5_variant_disease"},{"subj":"21362567-2#175#177#diseaseC0030567","pred":"source","obj":"DisGeNET5_variant_disease"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"21362567-3#27#32#gene120892","span":{"begin":479,"end":484},"obj":"gene120892"},{"id":"21362567-3#83#85#diseaseC0030567","span":{"begin":535,"end":537},"obj":"diseaseC0030567"}],"relations":[{"id":"27#32#gene12089283#85#diseaseC0030567","pred":"associated_with","subj":"21362567-3#27#32#gene120892","obj":"21362567-3#83#85#diseaseC0030567"}],"attributes":[{"subj":"21362567-3#27#32#gene120892","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21362567-3#83#85#diseaseC0030567","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"UseCases_ArguminSci_Discourse","denotations":[{"id":"T1","span":{"begin":0,"end":94},"obj":"DRI_Background"},{"id":"T2","span":{"begin":95,"end":212},"obj":"DRI_Background"},{"id":"T3","span":{"begin":213,"end":451},"obj":"DRI_Approach"},{"id":"T4","span":{"begin":452,"end":639},"obj":"DRI_Challenge"},{"id":"T5","span":{"begin":640,"end":782},"obj":"DRI_Outcome"},{"id":"T6","span":{"begin":783,"end":985},"obj":"DRI_Background"},{"id":"T7","span":{"begin":986,"end":1130},"obj":"DRI_Challenge"}],"attributes":[{"subj":"T1","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T2","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T3","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T4","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T5","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T6","pred":"source","obj":"UseCases_ArguminSci_Discourse"},{"subj":"T7","pred":"source","obj":"UseCases_ArguminSci_Discourse"}]},{"project":"PubMed_ArguminSci","denotations":[{"id":"T1","span":{"begin":95,"end":212},"obj":"DRI_Background"},{"id":"T2","span":{"begin":213,"end":451},"obj":"DRI_Approach"},{"id":"T3","span":{"begin":452,"end":639},"obj":"DRI_Challenge"},{"id":"T4","span":{"begin":640,"end":782},"obj":"DRI_Outcome"},{"id":"T5","span":{"begin":783,"end":985},"obj":"DRI_Background"},{"id":"T6","span":{"begin":986,"end":1130},"obj":"DRI_Challenge"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T2","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T3","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T4","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T5","pred":"source","obj":"PubMed_ArguminSci"},{"subj":"T6","pred":"source","obj":"PubMed_ArguminSci"}]},{"project":"c_corpus","denotations":[{"id":"T1","span":{"begin":0,"end":5},"obj":"PR:Q5S006"},{"id":"T2","span":{"begin":0,"end":5},"obj":"PR:000003033"},{"id":"T3","span":{"begin":0,"end":5},"obj":"PR:Q5S007"},{"id":"T4","span":{"begin":59,"end":73},"obj":"D004198"},{"id":"T5","span":{"begin":59,"end":73},"obj":"D004198"},{"id":"T10","span":{"begin":106,"end":125},"obj":"D010300"},{"id":"T11","span":{"begin":106,"end":125},"obj":"D010300"},{"id":"T14","span":{"begin":153,"end":157},"obj":"PR:Q9V853"},{"id":"T15","span":{"begin":180,"end":185},"obj":"D006801"},{"id":"T16","span":{"begin":298,"end":306},"obj":"SO:0000109"},{"id":"T18","span":{"begin":329,"end":336},"obj":"6308"},{"id":"T17","span":{"begin":329,"end":336},"obj":"CHEBI:15603"},{"id":"T20","span":{"begin":329,"end":336},"obj":"D007930"},{"id":"T21","span":{"begin":329,"end":336},"obj":"CHEBI:25017"},{"id":"T22","span":{"begin":329,"end":336},"obj":"D007930"},{"id":"T19","span":{"begin":329,"end":336},"obj":"SO:0001437"},{"id":"T23","span":{"begin":337,"end":341},"obj":"PR:Q9V3C5"},{"id":"T24","span":{"begin":349,"end":355},"obj":"D010770"},{"id":"T25","span":{"begin":359,"end":364},"obj":"PR:Q5S006"},{"id":"T26","span":{"begin":359,"end":364},"obj":"PR:000003033"},{"id":"T27","span":{"begin":359,"end":364},"obj":"PR:Q5S007"},{"id":"T28","span":{"begin":366,"end":370},"obj":"SO:0000704"},{"id":"T29","span":{"begin":399,"end":407},"obj":"SO:0000109"},{"id":"T30","span":{"begin":479,"end":484},"obj":"PR:Q5S006"},{"id":"T31","span":{"begin":479,"end":484},"obj":"PR:000003033"},{"id":"T32","span":{"begin":479,"end":484},"obj":"PR:Q5S007"},{"id":"T33","span":{"begin":485,"end":493},"obj":"SO:0000109"},{"id":"T34","span":{"begin":601,"end":608},"obj":"D004194"},{"id":"T35","span":{"begin":601,"end":608},"obj":"D004194"},{"id":"T36","span":{"begin":622,"end":626},"obj":"CHEBI:23888"},{"id":"T38","span":{"begin":764,"end":773},"obj":"P37379"},{"id":"T37","span":{"begin":764,"end":773},"obj":"D051843"},{"id":"T42","span":{"begin":774,"end":781},"obj":"PR:000000001"},{"id":"T39","span":{"begin":774,"end":781},"obj":"GO:0003675"},{"id":"T43","span":{"begin":774,"end":781},"obj":"SO:0000104"},{"id":"T40","span":{"begin":774,"end":781},"obj":"CHEBI:36080"},{"id":"T41","span":{"begin":774,"end":781},"obj":"CHEBI:11122"},{"id":"T46","span":{"begin":830,"end":839},"obj":"P55866"},{"id":"T47","span":{"begin":830,"end":839},"obj":"Q8MJC3"},{"id":"T48","span":{"begin":830,"end":839},"obj":"Q2PFV2"},{"id":"T49","span":{"begin":830,"end":839},"obj":"Q08DY9"},{"id":"T50","span":{"begin":830,"end":839},"obj":"Q5IS54"},{"id":"T51","span":{"begin":830,"end":839},"obj":"Q8MKI5"},{"id":"T52","span":{"begin":830,"end":839},"obj":"PR:000002312"},{"id":"T53","span":{"begin":830,"end":839},"obj":"Q8MJU1"},{"id":"T54","span":{"begin":830,"end":839},"obj":"Q60431"},{"id":"T55","span":{"begin":830,"end":839},"obj":"P42574"},{"id":"T56","span":{"begin":830,"end":839},"obj":"Q5IS99"},{"id":"T57","span":{"begin":830,"end":839},"obj":"Q95ND5"},{"id":"T58","span":{"begin":830,"end":839},"obj":"P70677"},{"id":"T59","span":{"begin":830,"end":839},"obj":"P55213"},{"id":"T45","span":{"begin":830,"end":839},"obj":"D053148"},{"id":"T60","span":{"begin":855,"end":865},"obj":"GO:0008219"},{"id":"T63","span":{"begin":911,"end":928},"obj":"5499"},{"id":"T64","span":{"begin":911,"end":928},"obj":"D006861"},{"id":"T65","span":{"begin":911,"end":928},"obj":"CHEBI:16240"},{"id":"T66","span":{"begin":911,"end":928},"obj":"D006861"},{"id":"T68","span":{"begin":930,"end":936},"obj":"C072553"},{"id":"T69","span":{"begin":930,"end":936},"obj":"CHEBI:75142"},{"id":"T70","span":{"begin":930,"end":936},"obj":"C072553"},{"id":"T72","span":{"begin":942,"end":959},"obj":"D016627"},{"id":"T73","span":{"begin":942,"end":959},"obj":"D016627"},{"id":"T74","span":{"begin":942,"end":959},"obj":"CHEBI:78741"}],"attributes":[{"subj":"T1","pred":"source","obj":"c_corpus"},{"subj":"T2","pred":"source","obj":"c_corpus"},{"subj":"T3","pred":"source","obj":"c_corpus"},{"subj":"T4","pred":"source","obj":"c_corpus"},{"subj":"T5","pred":"source","obj":"c_corpus"},{"subj":"T10","pred":"source","obj":"c_corpus"},{"subj":"T11","pred":"source","obj":"c_corpus"},{"subj":"T14","pred":"source","obj":"c_corpus"},{"subj":"T15","pred":"source","obj":"c_corpus"},{"subj":"T16","pred":"source","obj":"c_corpus"},{"subj":"T18","pred":"source","obj":"c_corpus"},{"subj":"T17","pred":"source","obj":"c_corpus"},{"subj":"T20","pred":"source","obj":"c_corpus"},{"subj":"T21","pred":"source","obj":"c_corpus"},{"subj":"T22","pred":"source","obj":"c_corpus"},{"subj":"T19","pred":"source","obj":"c_corpus"},{"subj":"T23","pred":"source","obj":"c_corpus"},{"subj":"T24","pred":"source","obj":"c_corpus"},{"subj":"T25","pred":"source","obj":"c_corpus"},{"subj":"T26","pred":"source","obj":"c_corpus"},{"subj":"T27","pred":"source","obj":"c_corpus"},{"subj":"T28","pred":"source","obj":"c_corpus"},{"subj":"T29","pred":"source","obj":"c_corpus"},{"subj":"T30","pred":"source","obj":"c_corpus"},{"subj":"T31","pred":"source","obj":"c_corpus"},{"subj":"T32","pred":"source","obj":"c_corpus"},{"subj":"T33","pred":"source","obj":"c_corpus"},{"subj":"T34","pred":"source","obj":"c_corpus"},{"subj":"T35","pred":"source","obj":"c_corpus"},{"subj":"T36","pred":"source","obj":"c_corpus"},{"subj":"T38","pred":"source","obj":"c_corpus"},{"subj":"T37","pred":"source","obj":"c_corpus"},{"subj":"T42","pred":"source","obj":"c_corpus"},{"subj":"T39","pred":"source","obj":"c_corpus"},{"subj":"T43","pred":"source","obj":"c_corpus"},{"subj":"T40","pred":"source","obj":"c_corpus"},{"subj":"T41","pred":"source","obj":"c_corpus"},{"subj":"T46","pred":"source","obj":"c_corpus"},{"subj":"T47","pred":"source","obj":"c_corpus"},{"subj":"T48","pred":"source","obj":"c_corpus"},{"subj":"T49","pred":"source","obj":"c_corpus"},{"subj":"T50","pred":"source","obj":"c_corpus"},{"subj":"T51","pred":"source","obj":"c_corpus"},{"subj":"T52","pred":"source","obj":"c_corpus"},{"subj":"T53","pred":"source","obj":"c_corpus"},{"subj":"T54","pred":"source","obj":"c_corpus"},{"subj":"T55","pred":"source","obj":"c_corpus"},{"subj":"T56","pred":"source","obj":"c_corpus"},{"subj":"T57","pred":"source","obj":"c_corpus"},{"subj":"T58","pred":"source","obj":"c_corpus"},{"subj":"T59","pred":"source","obj":"c_corpus"},{"subj":"T45","pred":"source","obj":"c_corpus"},{"subj":"T60","pred":"source","obj":"c_corpus"},{"subj":"T63","pred":"source","obj":"c_corpus"},{"subj":"T64","pred":"source","obj":"c_corpus"},{"subj":"T65","pred":"source","obj":"c_corpus"},{"subj":"T66","pred":"source","obj":"c_corpus"},{"subj":"T68","pred":"source","obj":"c_corpus"},{"subj":"T69","pred":"source","obj":"c_corpus"},{"subj":"T70","pred":"source","obj":"c_corpus"},{"subj":"T72","pred":"source","obj":"c_corpus"},{"subj":"T73","pred":"source","obj":"c_corpus"},{"subj":"T74","pred":"source","obj":"c_corpus"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Allie","color":"#93e8ec","default":true},{"id":"PubmedHPO","color":"#ecd593"},{"id":"DisGeNET","color":"#bb93ec"},{"id":"DisGeNET5_variant_disease","color":"#93eca1"},{"id":"DisGeNET5_gene_disease","color":"#ec939e"},{"id":"UseCases_ArguminSci_Discourse","color":"#93b8ec"},{"id":"PubMed_ArguminSci","color":"#d2ec93"},{"id":"c_corpus","color":"#ec93ec"}]}]}}