PubMed:18258746 JSON TXT

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PubTator4TogoVar

{"project":"PubTator4TogoVar","denotations":[{"id":"18258746_0","span":{"begin":423,"end":429},"obj":"ProteinMutation"},{"id":"18258746_1","span":{"begin":528,"end":534},"obj":"ProteinMutation"},{"id":"18258746_2","span":{"begin":620,"end":626},"obj":"ProteinMutation"},{"id":"18258746_3","span":{"begin":764,"end":770},"obj":"ProteinMutation"}],"attributes":[{"id":"18258746_0_ProteinMutation","pred":"proteinmutation","subj":"18258746_0","obj":"rs34637584"},{"id":"18258746_1_ProteinMutation","pred":"proteinmutation","subj":"18258746_1","obj":"rs34637584"},{"id":"18258746_2_ProteinMutation","pred":"proteinmutation","subj":"18258746_2","obj":"rs34637584"},{"id":"18258746_3_ProteinMutation","pred":"proteinmutation","subj":"18258746_3","obj":"rs34637584"}],"text":"A Drosophila model for LRRK2-linked parkinsonism.\nMutations in the leucine-rich repeat kinase (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. Previously, we and others found that expression of mutant LRRK2 causes neuronal degeneration in cell culture. Here we used the GAL4/UAS system to generate transgenic Drosophila expressing either wild-type human LRRK2 or LRRK2-G2019S, the most common mutation associated with PD. Expression of either wild-type human LRRK2 or LRRK2-G2019S in the photoreceptor cells caused retinal degeneration. Expression of LRRK2 or LRRK2-G2019S in neurons produced adult-onset selective loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Expression of mutant G2019S-LRRK2 caused a more severe parkinsonism-like phenotype than expression of equivalent levels of wild-type LRRK2. Treatment with l-DOPA improved mutant LRRK2-induced locomotor impairment but did not prevent the loss of tyrosine hydroxylase-positive neurons. To our knowledge, this is the first in vivo\"gain-of-function\" model which recapitulates several key features of LRRK2-linked human parkinsonism. These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention."}

c_corpus

PMID_GLOBAL

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":75,"end":79},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":124,"end":162},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":164,"end":166},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":472,"end":474},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":569,"end":589},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":1289,"end":1291},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0015404"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0011220"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0008199"},{"id":"A4","pred":"mondo_id","subj":"T3","obj":"0015873"},{"id":"A5","pred":"mondo_id","subj":"T3","obj":"0005180"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"0008199"},{"id":"A7","pred":"mondo_id","subj":"T6","obj":"0015873"},{"id":"A8","pred":"mondo_id","subj":"T6","obj":"0005180"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"0004580"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"0008199"},{"id":"A11","pred":"mondo_id","subj":"T10","obj":"0015873"},{"id":"A12","pred":"mondo_id","subj":"T10","obj":"0005180"}],"text":"A Drosophila model for LRRK2-linked parkinsonism.\nMutations in the leucine-rich repeat kinase (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. Previously, we and others found that expression of mutant LRRK2 causes neuronal degeneration in cell culture. Here we used the GAL4/UAS system to generate transgenic Drosophila expressing either wild-type human LRRK2 or LRRK2-G2019S, the most common mutation associated with PD. Expression of either wild-type human LRRK2 or LRRK2-G2019S in the photoreceptor cells caused retinal degeneration. Expression of LRRK2 or LRRK2-G2019S in neurons produced adult-onset selective loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Expression of mutant G2019S-LRRK2 caused a more severe parkinsonism-like phenotype than expression of equivalent levels of wild-type LRRK2. Treatment with l-DOPA improved mutant LRRK2-induced locomotor impairment but did not prevent the loss of tyrosine hydroxylase-positive neurons. To our knowledge, this is the first in vivo\"gain-of-function\" model which recapitulates several key features of LRRK2-linked human parkinsonism. These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention."}

UseCases_ArguminSci_Discourse

{"project":"UseCases_ArguminSci_Discourse","denotations":[{"id":"T1","span":{"begin":0,"end":49},"obj":"DRI_Approach"},{"id":"T2","span":{"begin":50,"end":196},"obj":"DRI_Challenge"},{"id":"T3","span":{"begin":197,"end":306},"obj":"DRI_Outcome"},{"id":"T4","span":{"begin":307,"end":475},"obj":"DRI_Outcome"},{"id":"T5","span":{"begin":476,"end":590},"obj":"DRI_Background"},{"id":"T6","span":{"begin":591,"end":742},"obj":"DRI_Background"},{"id":"T7","span":{"begin":743,"end":882},"obj":"DRI_Challenge"},{"id":"T8","span":{"begin":883,"end":1026},"obj":"DRI_Challenge"},{"id":"T9","span":{"begin":1027,"end":1171},"obj":"DRI_Outcome"},{"id":"T10","span":{"begin":1172,"end":1305},"obj":"DRI_Challenge"}],"text":"A Drosophila model for LRRK2-linked parkinsonism.\nMutations in the leucine-rich repeat kinase (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. Previously, we and others found that expression of mutant LRRK2 causes neuronal degeneration in cell culture. Here we used the GAL4/UAS system to generate transgenic Drosophila expressing either wild-type human LRRK2 or LRRK2-G2019S, the most common mutation associated with PD. Expression of either wild-type human LRRK2 or LRRK2-G2019S in the photoreceptor cells caused retinal degeneration. Expression of LRRK2 or LRRK2-G2019S in neurons produced adult-onset selective loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Expression of mutant G2019S-LRRK2 caused a more severe parkinsonism-like phenotype than expression of equivalent levels of wild-type LRRK2. Treatment with l-DOPA improved mutant LRRK2-induced locomotor impairment but did not prevent the loss of tyrosine hydroxylase-positive neurons. To our knowledge, this is the first in vivo\"gain-of-function\" model which recapitulates several key features of LRRK2-linked human parkinsonism. These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention."}

PubMed_ArguminSci

{"project":"PubMed_ArguminSci","denotations":[{"id":"T1","span":{"begin":50,"end":196},"obj":"DRI_Approach"},{"id":"T2","span":{"begin":197,"end":306},"obj":"DRI_Outcome"},{"id":"T3","span":{"begin":307,"end":475},"obj":"DRI_Outcome"},{"id":"T4","span":{"begin":476,"end":590},"obj":"DRI_Background"},{"id":"T5","span":{"begin":591,"end":742},"obj":"DRI_Background"},{"id":"T6","span":{"begin":743,"end":882},"obj":"DRI_Challenge"},{"id":"T7","span":{"begin":883,"end":1026},"obj":"DRI_Challenge"},{"id":"T8","span":{"begin":1027,"end":1171},"obj":"DRI_Outcome"},{"id":"T9","span":{"begin":1172,"end":1305},"obj":"DRI_Challenge"}],"text":"A Drosophila model for LRRK2-linked parkinsonism.\nMutations in the leucine-rich repeat kinase (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. Previously, we and others found that expression of mutant LRRK2 causes neuronal degeneration in cell culture. Here we used the GAL4/UAS system to generate transgenic Drosophila expressing either wild-type human LRRK2 or LRRK2-G2019S, the most common mutation associated with PD. Expression of either wild-type human LRRK2 or LRRK2-G2019S in the photoreceptor cells caused retinal degeneration. Expression of LRRK2 or LRRK2-G2019S in neurons produced adult-onset selective loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Expression of mutant G2019S-LRRK2 caused a more severe parkinsonism-like phenotype than expression of equivalent levels of wild-type LRRK2. Treatment with l-DOPA improved mutant LRRK2-induced locomotor impairment but did not prevent the loss of tyrosine hydroxylase-positive neurons. To our knowledge, this is the first in vivo\"gain-of-function\" model which recapitulates several key features of LRRK2-linked human parkinsonism. These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention."}