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

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 Hyun Cho; Inhee Mook-Jung

doi:10.1038/s41467-020-20440-5

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

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 Hyun Cho, Inhee Mook-Jung

Department of Brain Sciences

Research output: Contribution to journal › Article › peer-review

119 Scopus citations

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.

Original language	English
Article number	280
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20440-5
State	Published - 1 Dec 2021

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Publisher Copyright:
© 2021, The Author(s).

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10.1038/s41467-020-20440-5

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Park, J. C., Jang, S. Y., Lee, D., Lee, J., Kang, U., Chang, H., Kim, H. J., Han, S. H., Seo, J., Choi, M., Lee, D. Y., Byun, M. S., Yi, D., Cho, K. H., & Mook-Jung, I. (2021). A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids. Nature Communications, 12(1), Article 280. https://doi.org/10.1038/s41467-020-20440-5

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abstract = "Developing effective drugs for Alzheimer{\textquoteright}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.",

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

Abstract

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