Advanced human iPSC-based preclinical model for Parkinson’s disease with optogenetic alpha-synuclein aggregation
Cell Stem Cell, ISSN: 1934-5909, Vol: 30, Issue: 7, Page: 973-986.e11
2023
- 16Citations
- 55Captures
- 1Mentions
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations16
- Citation Indexes16
- 16
- CrossRef9
- Captures55
- Readers55
- 55
- Mentions1
- News Mentions1
- News1
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Advanced human iPSC-based preclinical model for Parkinson's disease with optogenetic alpha-synuclein aggregation.
Cell Stem Cell. 2023 Jun 9; Authors: Kim MS, Ra EA, Kweon SH, Seo BA, Ko HS, Oh Y, Lee G PubMed: 37339636 Submit Comment
Article Description
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.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S1934590923002114; http://dx.doi.org/10.1016/j.stem.2023.05.015; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85164200063&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/37339636; https://linkinghub.elsevier.com/retrieve/pii/S1934590923002114; https://dx.doi.org/10.1016/j.stem.2023.05.015
Elsevier BV
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