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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
  • 16
    Citations
  • 0
    Usage
  • 55
    Captures
  • 1
    Mentions
  • 9
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    16
  • Captures
    55
  • Mentions
    1
    • News Mentions
      1
      • News
        1
  • Social Media
    9
    • Shares, Likes & Comments
      9
      • Facebook
        9

Most Recent News

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.

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