干旱区生态环境知识资源中心(Arid): Advanced human iPSC-based preclinical model for Parkinson's disease with optogenetic alpha-synuclein aggregation

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DOI	10.1016/j.stem.2023.05.015
	Advanced human iPSC-based preclinical model for Parkinson's disease with optogenetic alpha-synuclein aggregation
	Kim, Min Seong; Ra, Eun A.; Kweon, Sin Ho; Seo, Bo Am; Ko, Han Seok; Oh, Yohan; Lee, Gabsang
通讯作者	Ko, HS ; Oh, Y ; Lee, GB
来源期刊	CELL STEM CELL
ISSN	1934-5909
EISSN	1875-9777
出版年	2023
卷号	30 期号:7 页码:973-+
英文摘要	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 a-synuclein (a-syn) aggregation induction system (OASIS) that rapidly induces a-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 charac-teristic PD phenotypes in a-syn preformed fibril models in vitro and in vivo by promoting autophagic clear-ance of pathological a-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.
类型	Article
语种	英语
开放获取类型	Bronze, Green Accepted
收录类别	SCI-E
WOS记录号	WOS:001042095800001
WOS关键词	MITOCHONDRIAL DYSFUNCTION ; SIGNAL INTEGRATION ; LEWY BODIES ; BRAIN ; PATHOLOGY ; AUTOPHAGY ; NEURONS ; CELLS ; MECHANISMS ; CANCER
WOS类目	Cell & Tissue Engineering ; Cell Biology
WOS研究方向	Cell Biology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/395720
推荐引用方式 GB/T 7714	Kim, Min Seong,Ra, Eun A.,Kweon, Sin Ho,et al. Advanced human iPSC-based preclinical model for Parkinson's disease with optogenetic alpha-synuclein aggregation[J],2023,30(7):973-+.
APA	Kim, Min Seong.,Ra, Eun A..,Kweon, Sin Ho.,Seo, Bo Am.,Ko, Han Seok.,...&Lee, Gabsang.(2023).Advanced human iPSC-based preclinical model for Parkinson's disease with optogenetic alpha-synuclein aggregation.CELL STEM CELL,30(7),973-+.
MLA	Kim, Min Seong,et al."Advanced human iPSC-based preclinical model for Parkinson's disease with optogenetic alpha-synuclein aggregation".CELL STEM CELL 30.7(2023):973-+.