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

被引：137

作者：

Park, Jong-Chan ^{[1
,2
,3
,4
]}

Jang, So-Yeong ^{[5
]}

Lee, Dongjoon ^{[1
,3
]}

Lee, Jeongha ^{[1
]}

Kang, Uiryong ^{[5
]}

Chang, Hongjun ^{[5
]}

Kim, Haeng Jun ^{[1
,3
]}

Han, Sun-Ho ^{[1
,2
,3
]}

Seo, Jinsoo ^{[6
]}

Choi, Murim ^{[1
]}

Lee, Dong Young ^{[7
,8
,9
]}

Byun, Min Soo ^{[10
]}

Yi, Dahyun ^{[7
]}

Cho, Kwang-Hyun ^{[5
]}

Mook-Jung, Inhee ^{[1
,2
,3
]}

机构：

[1] Seoul Natl Univ, Coll Med, Dept Biochem & Biomed Sci, Seoul 03080, South Korea

[2] Seoul Natl Univ, Coll Med, Med Res Ctr, Neurosci Res Inst, Seoul 03080, South Korea

[3] Seoul Natl Univ, Coll Med, SNU Dementia Res Ctr, Seoul 03080, South Korea

[4] UCL, Dept Neurodegenerat Dis, UCL Queen Sq Inst Neurol, London WC1N 3BG, England

[5] Korea Adv Inst Sci & Technol KAIST, Dept Bio & Brain Engn, Daejeon 34141, South Korea

[6] Daegu Gyeongbuk Inst Sci & Technol DGIST, Dept Brain & Cognit Sci, Daegu 42988, South Korea

[7] Seoul Natl Univ, Med Res Ctr, Inst Human Behav Med, Seoul 03080, South Korea

[8] Seoul Natl Univ, Coll Med, Dept Psychiat, Seoul 03080, South Korea

[9] Seoul Natl Univ Hosp, Dept Neuropsychiat, Seoul 03080, South Korea

[10] Seoul Natl Univ, Dept Neuropsychiat, Bundang Hosp, Seongnam 13620, South Korea

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

A-BETA; SYSTEMS BIOLOGY; R PACKAGE; DYNAMICS; MECHANISMS; MODEL; TAU; INHIBITION; PATHWAY; TRIALS;

D O I：

10.1038/s41467-020-20440-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 barrierpermeable 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.

引用

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