Potassium channel dysfunction in human neuronal models of Angelman syndrome-Reference-Cited by-同舟云学术

Potassium channel dysfunction in human neuronal models of Angelman syndrome

Published:2019-12-20 Issue:6472 Volume:366 Page:1486-1492
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Sun Alfred Xuyang¹²^ORCID,Yuan Qiang³⁴^ORCID,Fukuda Masahiro⁴^ORCID,Yu Weonjin⁴^ORCID,Yan Haidun⁵^ORCID,Lim Grace Gui Yin¹,Nai Mui Hoon⁶^ORCID,D’Agostino Giuseppe Alessandro⁷^ORCID,Tran Hoang-Dai²,Itahana Yoko⁸^ORCID,Wang Danlei¹^ORCID,Lokman Hidayat⁴^ORCID,Itahana Koji⁸^ORCID,Lim Stephanie Wai Lin⁴,Tang Jiong⁹^ORCID,Chang Ya Yin¹^ORCID,Zhang Menglan⁴^ORCID,Cook Stuart A.⁷^ORCID,Rackham Owen J. L.⁷^ORCID,Lim Chwee Teck⁶^ORCID,Tan Eng King¹⁴^ORCID,Ng Huck Hui²,Lim Kah Leong¹¹⁰¹¹^ORCID,Jiang Yong-Hui⁵,Je Hyunsoo Shawn⁴¹⁰^ORCID

Affiliation:

1. National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore.

2. Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.

3. Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.

4. Signature Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.

5. Department of Neurobiology, Duke University School of Medicine, Durham, NC 27710, USA.

6. Department of Biomedical Engineering, National University of Singapore, Singapore 117576, Singapore.

7. Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore.

8. Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, 169857, Singapore.

9. Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*STAR), Singapore 138667, Singapore.

10. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.

11. Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore 308232, Singapore.

Abstract

Hyperexcitable neurons in brain organoids Individuals with Angelman syndrome experience intellectual disability and seizures throughout their lives. In this condition, ubiquitin-mediated degradation of a key potassium channel is disrupted, allowing for the neuronal excitability and network synchronization that leads to seizure. Sun et al. used brain organoid technology to study what happens in human neurons with a mutation in a ubiquitin ligase that is implicated in Angelman syndrome. In these in vitro models and in a mouse model of Angelman syndrome, antagonists for the potassium channel normalized neuronal excitability. Science , this issue p. 1486

Funder

National Medical Research Council

Ministry of Education - Singapore

Duke-NUS Medical School

Duke NUS Medical School

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference47 articles.

1. Angelman syndrome — insights into a rare neurogenetic disorder

2. Angelman syndrome: insights into genomic imprinting and neurodevelopmental phenotypes