Cited 41 times in
Arylsulfatase A, a genetic modifier of Parkinson's disease, is an α-synuclein chaperone
DC Field | Value | Language |
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dc.contributor.author | 유한수 | - |
dc.contributor.author | 이필휴 | - |
dc.date.accessioned | 2022-08-23T02:43:38Z | - |
dc.date.available | 2022-08-23T02:43:38Z | - |
dc.date.issued | 2019-09 | - |
dc.identifier.issn | 0006-8950 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/189892 | - |
dc.description.abstract | Mutations in lysosomal genes increase the risk of neurodegenerative diseases, as is the case for Parkinson's disease. Here, we found that pathogenic and protective mutations in arylsulfatase A (ARSA), a gene responsible for metachromatic leukodystrophy, a lysosomal storage disorder, are linked to Parkinson's disease. Plasma ARSA protein levels were changed in Parkinson's disease patients. ARSA deficiency caused increases in α-synuclein aggregation and secretion, and increases in α-synuclein propagation in cells and nematodes. Despite being a lysosomal protein, ARSA directly interacts with α-synuclein in the cytosol. The interaction was more extensive with protective ARSA variant and less with pathogenic ARSA variant than wild-type. ARSA inhibited the in vitro fibrillation of α-synuclein in a dose-dependent manner. Ectopic expression of ARSA reversed the α-synuclein phenotypes in both cell and fly models of synucleinopathy, the effects correlating with the extent of the physical interaction between these molecules. Collectively, these results suggest that ARSA is a genetic modifier of Parkinson's disease pathogenesis, acting as a molecular chaperone for α-synuclein. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Oxford University Press | - |
dc.relation.isPartOf | BRAIN | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Adult | - |
dc.subject.MESH | Aged | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Animals, Genetically Modified | - |
dc.subject.MESH | Brain / enzymology | - |
dc.subject.MESH | Caenorhabditis elegans / genetics | - |
dc.subject.MESH | Caenorhabditis elegans / metabolism | - |
dc.subject.MESH | Caenorhabditis elegans Proteins / genetics | - |
dc.subject.MESH | Caenorhabditis elegans Proteins / metabolism | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Cerebroside-Sulfatase / blood | - |
dc.subject.MESH | Cerebroside-Sulfatase / genetics | - |
dc.subject.MESH | Cerebroside-Sulfatase / physiology* | - |
dc.subject.MESH | Dementia / blood | - |
dc.subject.MESH | Dementia / etiology | - |
dc.subject.MESH | Drosophila Proteins / deficiency | - |
dc.subject.MESH | Drosophila Proteins / genetics | - |
dc.subject.MESH | Drosophila Proteins / metabolism | - |
dc.subject.MESH | Drosophila melanogaster / genetics | - |
dc.subject.MESH | Drosophila melanogaster / metabolism | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Gene Knockout Techniques | - |
dc.subject.MESH | Genes, Dominant | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Middle Aged | - |
dc.subject.MESH | Molecular Chaperones / metabolism* | - |
dc.subject.MESH | Mutation, Missense* | - |
dc.subject.MESH | Parkinson Disease / genetics | - |
dc.subject.MESH | Parkinson Disease / metabolism* | - |
dc.subject.MESH | Parkinson Disease / psychology | - |
dc.subject.MESH | Pedigree | - |
dc.subject.MESH | Point Mutation* | - |
dc.subject.MESH | Protein Aggregation, Pathological / genetics | - |
dc.subject.MESH | Protein Interaction Mapping | - |
dc.subject.MESH | Recombinant Proteins / metabolism | - |
dc.subject.MESH | alpha-Synuclein / metabolism* | - |
dc.title | Arylsulfatase A, a genetic modifier of Parkinson's disease, is an α-synuclein chaperone | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Neurology (신경과학교실) | - |
dc.contributor.googleauthor | Jun Sung Lee | - |
dc.contributor.googleauthor | Kazuaki Kanai | - |
dc.contributor.googleauthor | Mari Suzuki | - |
dc.contributor.googleauthor | Woojin S Kim | - |
dc.contributor.googleauthor | Han Soo Yoo | - |
dc.contributor.googleauthor | YuHong Fu | - |
dc.contributor.googleauthor | Dong-Kyu Kim | - |
dc.contributor.googleauthor | Byung Chul Jung | - |
dc.contributor.googleauthor | Minsun Choi | - |
dc.contributor.googleauthor | Kyu Won Oh | - |
dc.contributor.googleauthor | Yuanzhe Li | - |
dc.contributor.googleauthor | Mitsuyoshi Nakatani | - |
dc.contributor.googleauthor | Tomoko Nakazato | - |
dc.contributor.googleauthor | Satoko Sekimoto | - |
dc.contributor.googleauthor | Manabu Funayama | - |
dc.contributor.googleauthor | Hiroyo Yoshino | - |
dc.contributor.googleauthor | Shin-Ichiro Kubo | - |
dc.contributor.googleauthor | Kenya Nishioka | - |
dc.contributor.googleauthor | Ryusuke Sakai | - |
dc.contributor.googleauthor | Morio Ueyama | - |
dc.contributor.googleauthor | Hideki Mochizuki | - |
dc.contributor.googleauthor | He-Jin Lee | - |
dc.contributor.googleauthor | Sergio Pablo Sardi | - |
dc.contributor.googleauthor | Glenda M Halliday | - |
dc.contributor.googleauthor | Yoshitaka Nagai | - |
dc.contributor.googleauthor | Phil Hyu Lee | - |
dc.contributor.googleauthor | Nobutaka Hattori | - |
dc.contributor.googleauthor | Seung-Jae Lee | - |
dc.identifier.doi | 10.1093/brain/awz205 | - |
dc.contributor.localId | A05367 | - |
dc.contributor.localId | A03270 | - |
dc.relation.journalcode | J00385 | - |
dc.identifier.eissn | 1460-2156 | - |
dc.identifier.pmid | 31312839 | - |
dc.identifier.url | https://academic.oup.com/brain/article/142/9/2845/5532496?login=true | - |
dc.subject.keyword | Parkinson’s disease | - |
dc.subject.keyword | arylsulfatase A | - |
dc.subject.keyword | molecular chaperone | - |
dc.subject.keyword | protein aggregation and propagation | - |
dc.subject.keyword | α-synuclein | - |
dc.contributor.alternativeName | Yoo, Han Soo | - |
dc.contributor.affiliatedAuthor | 유한수 | - |
dc.contributor.affiliatedAuthor | 이필휴 | - |
dc.citation.volume | 142 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 2845 | - |
dc.citation.endPage | 2859 | - |
dc.identifier.bibliographicCitation | BRAIN, Vol.142(9) : 2845-2859, 2019-09 | - |
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