Advanced human iPSC-based preclinical model for Parkinson’s disease with optogenetic alpha-synuclein aggregation
DC Field | Value | Language |
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dc.contributor.author | Kim, Min Seong | - |
dc.contributor.author | Ra, Eun A. | - |
dc.contributor.author | Kweon, Sin Ho | - |
dc.contributor.author | Seo, Bo Am | - |
dc.contributor.author | Ko, Han Seok | - |
dc.contributor.author | Oh, Yohan | - |
dc.contributor.author | Lee, Gabsang | - |
dc.date.accessioned | 2023-07-24T10:01:22Z | - |
dc.date.available | 2023-07-24T10:01:22Z | - |
dc.date.created | 2023-06-30 | - |
dc.date.issued | 2023-07 | - |
dc.identifier.issn | 1934-5909 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/187559 | - |
dc.description.abstract | Human induced pluripotent stem cells (hiPSCs) offer advantages for disease modeling and drug discovery. However, recreating innate cellular pathologies, particularly in late-onset neurodegenerative diseases with accumulated protein aggregates including Parkinson's disease (PD), has been challenging. To overcome this barrier, we developed an optogenetics-assisted α-synuclein (α-syn) aggregation induction system (OASIS) that rapidly induces α-syn aggregates and toxicity in PD hiPSC-midbrain dopaminergic neurons and midbrain organoids. Our OASIS-based primary compound screening with SH-SY5Y cells identified 5 candidates that were secondarily validated with OASIS PD hiPSC-midbrain dopaminergic neurons and midbrain organoids, leading us to finally select BAG956. Furthermore, BAG956 significantly reverses characteristic PD phenotypes in α-syn preformed fibril models in vitro and in vivo by promoting autophagic clearance of pathological α-syn aggregates. Following the FDA Modernization Act 2.0's emphasis on alternative non-animal testing methods, our OASIS can serve as an animal-free preclinical test model (newly termed "nonclinical test") for the synucleinopathy drug development. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | Cell Press | - |
dc.title | Advanced human iPSC-based preclinical model for Parkinson’s disease with optogenetic alpha-synuclein aggregation | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Oh, Yohan | - |
dc.identifier.doi | 10.1016/j.stem.2023.05.015 | - |
dc.identifier.scopusid | 2-s2.0-85164200063 | - |
dc.identifier.wosid | 001042095800001 | - |
dc.identifier.bibliographicCitation | Cell Stem Cell, v.30, no.7, pp.973 - 986 | - |
dc.relation.isPartOf | Cell Stem Cell | - |
dc.citation.title | Cell Stem Cell | - |
dc.citation.volume | 30 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 973 | - |
dc.citation.endPage | 986 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Cell & Tissue Engineering | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | MITOCHONDRIAL DYSFUNCTION | - |
dc.subject.keywordPlus | SIGNAL INTEGRATION | - |
dc.subject.keywordPlus | LEWY BODIES | - |
dc.subject.keywordPlus | BRAIN | - |
dc.subject.keywordPlus | PATHOLOGY | - |
dc.subject.keywordPlus | AUTOPHAGY | - |
dc.subject.keywordPlus | NEURONS | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordAuthor | Parkinson’s disease | - |
dc.subject.keywordAuthor | alpha-synuclein | - |
dc.subject.keywordAuthor | dopaminergic neurons | - |
dc.subject.keywordAuthor | human pluripotent stem cell | - |
dc.subject.keywordAuthor | opto-alpha-synuclein | - |
dc.subject.keywordAuthor | optogenetics | - |
dc.subject.keywordAuthor | organoid | - |
dc.subject.keywordAuthor | protein aggregation | - |
dc.subject.keywordAuthor | α-syn PFFs | - |
dc.subject.keywordAuthor | α-synuclein preformed fibrils | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S1934590923002114?via%3Dihub | - |
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