Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Ham, Sangwoo | ko |
dc.contributor.author | Yun, Seung Pil | ko |
dc.contributor.author | Kim, Hyojung | ko |
dc.contributor.author | Kim, Donghoon | ko |
dc.contributor.author | Seo, Bo Am | ko |
dc.contributor.author | Kim, Heejeong | ko |
dc.contributor.author | Shin, Jeong-Yong | ko |
dc.contributor.author | Dar, Mohamad | ko |
dc.contributor.author | Lee, Gum Hwa | ko |
dc.contributor.author | Lee, Yun Il | ko |
dc.contributor.author | Kim, Doyeun | ko |
dc.contributor.author | Kim, Sunghoon | ko |
dc.contributor.author | Kweon, Hee-Seok | ko |
dc.contributor.author | Shin, Joo-Ho | ko |
dc.contributor.author | Ko, Han Seok | ko |
dc.contributor.author | Lee, Yunjong | ko |
dc.date.accessioned | 2021-01-22T07:29:08Z | - |
dc.date.available | 2021-01-22T07:29:08Z | - |
dc.date.created | 2020-11-26 | - |
dc.date.issued | 2020-11 | - |
dc.identifier.citation | Science Translational Medicine, v.12, no.569, pp.eaax0091 | - |
dc.identifier.issn | 1946-6234 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/12770 | - |
dc.description.abstract | Lewy bodies are pathological protein inclusions present in the brain of patients with Parkinson's disease (PD). These inclusions consist mainly of α-synuclein with associated proteins, such as parkin and its substrate aminoacyl transfer RNA synthetase complex-interacting multifunctional protein-2 (AIMP2). Although AIMP2 has been suggested to be toxic to dopamine neurons, its roles in α-synuclein aggregation and PD pathogenesis are largely unknown. Here, we found that AIMP2 exhibits a self-aggregating property. The AIMP2 aggregate serves as a seed to increase α-synuclein aggregation via specific and direct binding to the α-synuclein monomer. The coexpression of AIMP2 and α-synuclein in cell cultures and in vivo resulted in the rapid formation of α-synuclein aggregates with a corresponding increase in toxicity. Moreover, accumulated AIMP2 in mouse brain was largely redistributed to insoluble fractions, correlating with the α-synuclein pathology. Last, we found that α-synuclein preformed fibril (PFF) seeding, adult Parkin deletion, or oxidative stress triggered a redistribution of both AIMP2 and α-synuclein into insoluble fraction in cells and in vivo. Supporting the pathogenic role of AIMP2, AIMP2 knockdown ameliorated the α-synuclein aggregation and dopaminergic cell death in response to PFF or 6-hydroxydopamine treatment. Together, our results suggest that AIMP2 plays a pathological role in the aggregation of α-synuclein in mice. Because AIMP2 insolubility and coaggregation with α-synuclein have been seen in the PD Lewy body, targeting pathologic AIMP2 aggregation might be useful as a therapeutic strategy for neurodegenerative α-synucleinopathies. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works | - |
dc.language | English | - |
dc.publisher | American Association for the Advancement of Science | - |
dc.title | Amyloid-like oligomerization of AIMP2 contributes to alpha-synuclein interaction and Lewy-like inclusion | - |
dc.type | Article | - |
dc.identifier.doi | 10.1126/scitranslmed.aax0091 | - |
dc.identifier.wosid | 000590468700005 | - |
dc.identifier.scopusid | 2-s2.0-85096081434 | - |
dc.type.local | Article(Overseas) | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.contributor.nonIdAuthor | Ham, Sangwoo | - |
dc.contributor.nonIdAuthor | Yun, Seung Pil | - |
dc.contributor.nonIdAuthor | Kim, Hyojung | - |
dc.contributor.nonIdAuthor | Kim, Donghoon | - |
dc.contributor.nonIdAuthor | Seo, Bo Am | - |
dc.contributor.nonIdAuthor | Kim, Heejeong | - |
dc.contributor.nonIdAuthor | Shin, Jeong-Yong | - |
dc.contributor.nonIdAuthor | Dar, Mohamad | - |
dc.contributor.nonIdAuthor | Lee, Gum Hwa | - |
dc.contributor.nonIdAuthor | Kim, Doyeun | - |
dc.contributor.nonIdAuthor | Kim, Sunghoon | - |
dc.contributor.nonIdAuthor | Kweon, Hee-Seok | - |
dc.contributor.nonIdAuthor | Shin, Joo-Ho | - |
dc.contributor.nonIdAuthor | Ko, Han Seok | - |
dc.contributor.nonIdAuthor | Lee, Yunjong | - |
dc.identifier.citationVolume | 12 | - |
dc.identifier.citationNumber | 569 | - |
dc.identifier.citationStartPage | eaax0091 | - |
dc.identifier.citationTitle | Science Translational Medicine | - |
dc.type.journalArticle | Article | - |
dc.description.isOpenAccess | N | - |
dc.subject.keywordPlus | RECESSIVE JUVENILE PARKINSONISM | - |
dc.subject.keywordPlus | RNA SYNTHETASE COFACTOR | - |
dc.subject.keywordPlus | DOWN-REGULATION | - |
dc.subject.keywordPlus | BODY FORMATION | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | AGGREGATION | - |
dc.subject.keywordPlus | NEURODEGENERATION | - |
dc.subject.keywordPlus | PHOSPHORYLATION | - |
dc.subject.keywordPlus | BODIES | - |
dc.contributor.affiliatedAuthor | Lee, Yun Il | - |
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