Cited 21 times in
LIN28A loss of function is associated with Parkinson's disease pathogenesis
DC Field | Value | Language |
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dc.contributor.author | 김형범 | - |
dc.date.accessioned | 2022-08-19T06:24:18Z | - |
dc.date.available | 2022-08-19T06:24:18Z | - |
dc.date.issued | 2019-12 | - |
dc.identifier.issn | 0261-4189 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/189139 | - |
dc.description.abstract | Parkinson's disease (PD) is neurodegenerative movement disorder characterized by degeneration of midbrain-type dopamine (mDA) neurons in the substantia nigra (SN). The RNA-binding protein Lin28 plays a role in neuronal stem cell development and neuronal differentiation. In this study, we reveal that Lin28 conditional knockout (cKO) mice show degeneration of mDA neurons in the SN, as well as PD-related behavioral deficits. We identify a loss-of-function variant of LIN28A (R192G substitution) in two early-onset PD patients. Using an isogenic human embryonic stem cell (hESC)/human induced pluripotent stem cell (hiPSC)-based disease model, we find that the Lin28 R192G variant leads to developmental defects and PD-related phenotypes in mDA neuronal cells that can be rescued by expression of wild-type Lin28A. Cell transplantation experiments in PD model rats show that correction of the LIN28A variant in the donor patient (pt)-hiPSCs leads to improved behavioral phenotypes. Our data link LIN28A to PD pathogenesis and suggest future personalized medicine targeting this variant in patients. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Wiley Blackwell | - |
dc.relation.isPartOf | EMBO JOURNAL | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Behavior, Animal | - |
dc.subject.MESH | Cell Transplantation | - |
dc.subject.MESH | Disease Models, Animal | - |
dc.subject.MESH | Dopamine / metabolism | - |
dc.subject.MESH | Dopaminergic Neurons / physiology | - |
dc.subject.MESH | Embryonic Stem Cells / physiology | - |
dc.subject.MESH | Gene Editing | - |
dc.subject.MESH | Genetic Predisposition to Disease | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Induced Pluripotent Stem Cells / physiology | - |
dc.subject.MESH | Induced Pluripotent Stem Cells / transplantation | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Knockout | - |
dc.subject.MESH | Mutation | - |
dc.subject.MESH | Neural Stem Cells / physiology | - |
dc.subject.MESH | Neural Stem Cells / transplantation | - |
dc.subject.MESH | Parkinson Disease / genetics | - |
dc.subject.MESH | Parkinson Disease / metabolism* | - |
dc.subject.MESH | RNA-Binding Proteins / genetics* | - |
dc.subject.MESH | RNA-Binding Proteins / physiology* | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Stem Cell Transplantation | - |
dc.subject.MESH | Substantia Nigra / metabolism* | - |
dc.title | LIN28A loss of function is associated with Parkinson's disease pathogenesis | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pharmacology (약리학교실) | - |
dc.contributor.googleauthor | Mi-Yoon Chang | - |
dc.contributor.googleauthor | Boram Oh | - |
dc.contributor.googleauthor | Jang-Eun Choi | - |
dc.contributor.googleauthor | Yanuar Alan Sulistio | - |
dc.contributor.googleauthor | Hye-Ji Woo | - |
dc.contributor.googleauthor | Ayoung Jo | - |
dc.contributor.googleauthor | Jinil Kim | - |
dc.contributor.googleauthor | Eun-Hee Kim | - |
dc.contributor.googleauthor | Seung Won Kim | - |
dc.contributor.googleauthor | Jungwook Hwang | - |
dc.contributor.googleauthor | Jungyun Park | - |
dc.contributor.googleauthor | Jae-Jin Song | - |
dc.contributor.googleauthor | Oh-Chan Kwon | - |
dc.contributor.googleauthor | Hyongbum Henry Kim | - |
dc.contributor.googleauthor | Young-Hoon Kim | - |
dc.contributor.googleauthor | Joo Yeon Ko | - |
dc.contributor.googleauthor | Jun Young Heo | - |
dc.contributor.googleauthor | Min Joung Lee | - |
dc.contributor.googleauthor | Moses Lee | - |
dc.contributor.googleauthor | Murim Choi | - |
dc.contributor.googleauthor | Sun Ju Chung | - |
dc.contributor.googleauthor | Hyun-Seob Lee | - |
dc.contributor.googleauthor | Sang-Hun Lee | - |
dc.identifier.doi | 10.15252/embj.2018101196 | - |
dc.contributor.localId | A01148 | - |
dc.relation.journalcode | J00763 | - |
dc.identifier.eissn | 1460-2075 | - |
dc.identifier.pmid | 31750563 | - |
dc.subject.keyword | human disease model | - |
dc.subject.keyword | human pluripotent stem cells | - |
dc.subject.keyword | Lin28 | - |
dc.subject.keyword | loss-of-function mutation | - |
dc.subject.keyword | Parkinson's disease | - |
dc.contributor.alternativeName | Kim, Hyongbum | - |
dc.contributor.affiliatedAuthor | 김형범 | - |
dc.citation.volume | 38 | - |
dc.citation.number | 24 | - |
dc.citation.startPage | e101196 | - |
dc.identifier.bibliographicCitation | EMBO JOURNAL, Vol.38(24) : e101196, 2019-12 | - |
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