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A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids

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  • Jong-Chan Park

    (College of Medicine, Seoul National University
    Neuroscience Research Institute, Medical Research Center, College of Medicine, Seoul National University
    SNU Dementia Research Center, College of Medicine, Seoul National University
    Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London)

  • So-Yeong Jang

    (Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST))

  • Dongjoon Lee

    (College of Medicine, Seoul National University
    SNU Dementia Research Center, College of Medicine, Seoul National University)

  • Jeongha Lee

    (College of Medicine, Seoul National University)

  • Uiryong Kang

    (Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST))

  • Hongjun Chang

    (Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST))

  • Haeng Jun Kim

    (College of Medicine, Seoul National University
    SNU Dementia Research Center, College of Medicine, Seoul National University)

  • Sun-Ho Han

    (College of Medicine, Seoul National University
    Neuroscience Research Institute, Medical Research Center, College of Medicine, Seoul National University
    SNU Dementia Research Center, College of Medicine, Seoul National University)

  • Jinsoo Seo

    (Department of Brain and Cognitive Science, Daegu Gyeongbuk Institute of Sciences and Technology (DGIST))

  • Murim Choi

    (College of Medicine, Seoul National University)

  • Dong Young Lee

    (Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University
    Department of Psychiatry, College of medicine, Seoul National University
    Department of Neuropsychiatry, Seoul National University Hospital)

  • Min Soo Byun

    (Department of Neuropsychiatry, Seoul National University Bundang Hospital)

  • Dahyun Yi

    (Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University)

  • Kwang-Hyun Cho

    (Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST))

  • Inhee Mook-Jung

    (College of Medicine, Seoul National University
    Neuroscience Research Institute, Medical Research Center, College of Medicine, Seoul National University
    SNU Dementia Research Center, College of Medicine, Seoul National University)

Abstract

Developing effective drugs for Alzheimer’s disease (AD), the most common cause of dementia, has been difficult because of complicated pathogenesis. Here, we report an efficient, network-based drug-screening platform developed by integrating mathematical modeling and the pathological features of AD with human iPSC-derived cerebral organoids (iCOs), including CRISPR-Cas9-edited isogenic lines. We use 1300 organoids from 11 participants to build a high-content screening (HCS) system and test blood–brain barrier-permeable FDA-approved drugs. Our study provides a strategy for precision medicine through the convergence of mathematical modeling and a miniature pathological brain model using iCOs.

Suggested Citation

  • Jong-Chan Park & So-Yeong Jang & Dongjoon Lee & Jeongha Lee & Uiryong Kang & Hongjun Chang & Haeng Jun Kim & Sun-Ho Han & Jinsoo Seo & Murim Choi & Dong Young Lee & Min Soo Byun & Dahyun Yi & Kwang-Hy, 2021. "A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20440-5
    DOI: 10.1038/s41467-020-20440-5
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    Cited by:

    1. Patricia R. Pitrez & Luis M. Monteiro & Oliver Borgogno & Xavier Nissan & Jerome Mertens & Lino Ferreira, 2024. "Cellular reprogramming as a tool to model human aging in a dish," Nature Communications, Nature, vol. 15(1), pages 1-11, December.

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