PubMed:26744328 JSON TXT

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PubTator4TogoVar

{"project":"PubTator4TogoVar","denotations":[{"id":"26744328_0","span":{"begin":1013,"end":1019},"obj":"ProteinMutation"},{"id":"26744328_1","span":{"begin":1145,"end":1151},"obj":"ProteinMutation"}],"attributes":[{"id":"26744328_0_ProteinMutation","pred":"proteinmutation","subj":"26744328_0","obj":"rs34637584"},{"id":"26744328_1_ProteinMutation","pred":"proteinmutation","subj":"26744328_1","obj":"rs34637584"}],"text":"Synphilin-1 attenuates mutant LRRK2-induced neurodegeneration in Parkinson's disease models.\nMutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant Parkinsonism with pleomorphic pathology including deposits of aggregated protein and neuronal degeneration. The pathogenesis of LRRK2-linked Parkinson's disease (PD) is not fully understood. Here, using co-immunoprecipitation, we found that LRRK2 interacted with synphilin-1 (SP1), a cytoplasmic protein that interacts with α-synuclein and has implications in PD pathogenesis. LRRK2 interacted with the N-terminus of SP1 whereas SP1 predominantly interacted with the C-terminus of LRRK2, including kinase domain. Co-expression of SP1 with LRRK2 increased LRRK2-induced cytoplasmic aggregation in cultured cells. Moreover, SP1 also attenuated mutant LRRK2-induced toxicity and reduced LRRK2 kinase activity in cultured cells. Knockdown of SP1 by siRNA enhanced LRRK2 neuronal toxicity. In vivo Drosophila studies, co-expression of SP1 and mutant G2019S-LRRK2 in double transgenic Drosophila increased survival and improved locomotor activity. Expression of SP1 protects against G2019S-LRRK2-induced dopamine neuron loss and reduced LRRK2 phosphorylation in double transgenic fly brains. Our findings demonstrate that SP1 attenuates mutant LRRK2-induced PD-like phenotypes and plays a neural protective role."}

c_corpus

PubMed_ArguminSci

{"project":"PubMed_ArguminSci","denotations":[{"id":"T1","span":{"begin":93,"end":275},"obj":"DRI_Outcome"},{"id":"T2","span":{"begin":276,"end":358},"obj":"DRI_Background"},{"id":"T3","span":{"begin":359,"end":544},"obj":"DRI_Approach"},{"id":"T4","span":{"begin":545,"end":680},"obj":"DRI_Outcome"},{"id":"T5","span":{"begin":681,"end":779},"obj":"DRI_Background"},{"id":"T6","span":{"begin":780,"end":892},"obj":"DRI_Background"},{"id":"T7","span":{"begin":893,"end":952},"obj":"DRI_Background"},{"id":"T8","span":{"begin":953,"end":1109},"obj":"DRI_Background"},{"id":"T9","span":{"begin":1110,"end":1253},"obj":"DRI_Outcome"},{"id":"T10","span":{"begin":1254,"end":1305},"obj":"DRI_Outcome"},{"id":"T11","span":{"begin":1328,"end":1374},"obj":"DRI_Outcome"}],"text":"Synphilin-1 attenuates mutant LRRK2-induced neurodegeneration in Parkinson's disease models.\nMutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant Parkinsonism with pleomorphic pathology including deposits of aggregated protein and neuronal degeneration. The pathogenesis of LRRK2-linked Parkinson's disease (PD) is not fully understood. Here, using co-immunoprecipitation, we found that LRRK2 interacted with synphilin-1 (SP1), a cytoplasmic protein that interacts with α-synuclein and has implications in PD pathogenesis. LRRK2 interacted with the N-terminus of SP1 whereas SP1 predominantly interacted with the C-terminus of LRRK2, including kinase domain. Co-expression of SP1 with LRRK2 increased LRRK2-induced cytoplasmic aggregation in cultured cells. Moreover, SP1 also attenuated mutant LRRK2-induced toxicity and reduced LRRK2 kinase activity in cultured cells. Knockdown of SP1 by siRNA enhanced LRRK2 neuronal toxicity. In vivo Drosophila studies, co-expression of SP1 and mutant G2019S-LRRK2 in double transgenic Drosophila increased survival and improved locomotor activity. Expression of SP1 protects against G2019S-LRRK2-induced dopamine neuron loss and reduced LRRK2 phosphorylation in double transgenic fly brains. Our findings demonstrate that SP1 attenuates mutant LRRK2-induced PD-like phenotypes and plays a neural protective role."}

DisGeNET5_gene_disease

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"26744328-0#0#11#gene9627","span":{"begin":0,"end":11},"obj":"gene9627"},{"id":"26744328-0#30#35#gene120892","span":{"begin":30,"end":35},"obj":"gene120892"},{"id":"26744328-0#65#84#diseaseC0030567","span":{"begin":65,"end":84},"obj":"diseaseC0030567"},{"id":"26744328-1#13#41#gene120892","span":{"begin":106,"end":134},"obj":"gene120892"},{"id":"26744328-1#43#48#gene120892","span":{"begin":136,"end":141},"obj":"gene120892"},{"id":"26744328-1#56#87#diseaseC0752098","span":{"begin":149,"end":180},"obj":"diseaseC0752098"},{"id":"26744328-3#93#112#gene8548","span":{"begin":452,"end":471},"obj":"gene8548"},{"id":"26744328-3#169#171#diseaseC0030567","span":{"begin":528,"end":530},"obj":"diseaseC0030567"}],"relations":[{"id":"0#11#gene962765#84#diseaseC0030567","pred":"associated_with","subj":"26744328-0#0#11#gene9627","obj":"26744328-0#65#84#diseaseC0030567"},{"id":"30#35#gene12089265#84#diseaseC0030567","pred":"associated_with","subj":"26744328-0#30#35#gene120892","obj":"26744328-0#65#84#diseaseC0030567"},{"id":"13#41#gene12089256#87#diseaseC0752098","pred":"associated_with","subj":"26744328-1#13#41#gene120892","obj":"26744328-1#56#87#diseaseC0752098"},{"id":"43#48#gene12089256#87#diseaseC0752098","pred":"associated_with","subj":"26744328-1#43#48#gene120892","obj":"26744328-1#56#87#diseaseC0752098"},{"id":"93#112#gene8548169#171#diseaseC0030567","pred":"associated_with","subj":"26744328-3#93#112#gene8548","obj":"26744328-3#169#171#diseaseC0030567"}],"text":"Synphilin-1 attenuates mutant LRRK2-induced neurodegeneration in Parkinson's disease models.\nMutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant Parkinsonism with pleomorphic pathology including deposits of aggregated protein and neuronal degeneration. The pathogenesis of LRRK2-linked Parkinson's disease (PD) is not fully understood. Here, using co-immunoprecipitation, we found that LRRK2 interacted with synphilin-1 (SP1), a cytoplasmic protein that interacts with α-synuclein and has implications in PD pathogenesis. LRRK2 interacted with the N-terminus of SP1 whereas SP1 predominantly interacted with the C-terminus of LRRK2, including kinase domain. Co-expression of SP1 with LRRK2 increased LRRK2-induced cytoplasmic aggregation in cultured cells. Moreover, SP1 also attenuated mutant LRRK2-induced toxicity and reduced LRRK2 kinase activity in cultured cells. Knockdown of SP1 by siRNA enhanced LRRK2 neuronal toxicity. In vivo Drosophila studies, co-expression of SP1 and mutant G2019S-LRRK2 in double transgenic Drosophila increased survival and improved locomotor activity. Expression of SP1 protects against G2019S-LRRK2-induced dopamine neuron loss and reduced LRRK2 phosphorylation in double transgenic fly brains. Our findings demonstrate that SP1 attenuates mutant LRRK2-induced PD-like phenotypes and plays a neural protective role."}

PubMed:26744328 JSONTXT

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PubTator4TogoVar

c_corpus

PubMed_ArguminSci

DisGeNET5_gene_disease

PubMed:26744328 JSON TXT