Disrupted-in-Schizophrenia-1 (DISC1) protein disturbs neural function in multiple disease-risk pathways
Shao, Lisha3; Lu, Binyan2; Wen, Zhexing1,9,10; Teng, Shaolei8; Wang, Lingling; Zhao, Yi; Wang, Liyuan; Ishizuka, Koko7; Xu, Xiufeng6; Sawa, Akira7
刊名HUMAN MOLECULAR GENETICS
2017
卷号26期号:14页码:2634-2648
ISSN号0964-6906
DOI10.3897/phytokeys.86.20859
文献子类Article
英文摘要Although the genetic contribution is under debate, biological studies in multiple mouse models have suggested that the Disrupted-in-Schizophrenia-1 (DISC1) protein may contribute to susceptibility to psychiatric disorders. In the present study, we took the advantages of the Drosophila model to dissect the molecular pathways that can be affected by DISC1 in the context of pathology-related phenotypes. We found that three pathways that include the homologs of Drosophila Dys, Trio, and Shot were downregulated by introducing a C-terminal truncated mutant DISC1. Consistently, these three molecules were downregulated in the induced pluripotent stem cell-derived forebrain neurons from the subjects carrying a frameshift deletion in DISC1 C-terminus. Importantly, the three pathways were underscored in the pathophysiology of psychiatric disorders in bioinformatics analysis. Taken together, our findings are in line with the polygenic theory of psychiatric disorders.
学科主题Plant Sciences
电子版国际标准刊号1460-2083
出版地OXFORD
WOS关键词DE-NOVO MUTATIONS ; PROGENITOR PROLIFERATION ; NEUROTRANSMITTER RELEASE ; DROSOPHILA-MELANOGASTER ; NEUROMUSCULAR-JUNCTION ; PSYCHIATRIC-DISORDERS ; MENTAL-ILLNESS ; SCHIZOPHRENIA ; GENE ; DYSTROPHIN
语种英语
出版者OXFORD UNIV PRESS
WOS记录号WOS:000411804800002
资助机构National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [91332207, 91632301] ; National Basic Research Project (973 program) of Ministry of Science and Technology of China [2013cb835100] ; Beijing Municipal Science & Technology CommissionBeijing Municipal Science & Technology Commission [Z161100002616010] ; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NS047344, NS048271, MH105128] ; MSCRF [MH-084018, MH-094268, MH-069853, MH-085226, MH-088753, MH-092443] ; Silvo O. Conte Center [DA-040127] ; NARSADNARSAD ; Stanley ; RUSK ; S-R Foundations ; NATIONAL INSTITUTE OF MENTAL HEALTHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01MH069853, P20MH084018, R01MH105660, RC1MH088753, R21MH085226, P50MH094268, R01MH092443, R01MH105128] Funding Source: NIH RePORTER ; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R56NS047344, R01NS047344, R37NS047344, R01NS048271] Funding Source: NIH RePORTER ; NATIONAL INSTITUTE ON DRUG ABUSEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA)European Commission [R21DA040127] Funding Source: NIH RePORTER ; National Institute on Minority Health and Health DisparitiesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Minority Health & Health Disparities (NIMHD) [G12MD007597] Funding Source: NIH RePORTER
内容类型期刊论文
源URL[http://ir.ibcas.ac.cn/handle/2S10CLM1/22102]  
专题系统与进化植物学国家重点实验室
作者单位1.Chinese Acad Sci, Inst Bot, State Key Lab Systemat & Evolutionary Bot, Beijing 100093, Peoples R China
2.Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA
3.Tsinghua Univ, IDG McGovern Inst Brain Res, Sch Life Sci, Tsinghua Peking Ctr Life Sci,MOE Key Lab Prot Sci, Beijing 100084, Peoples R China
4.Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA
5.Kunming Med Univ, Affiliated Hosp 1, Dept Psychiat, Kunming 650032, Peoples R China
6.Johns Hopkins Univ, Sch Med, Dept Psychiat, Mol Psychiat Program, Baltimore, MD 21287 USA
7.Howard Univ, Dept Biol, Washington, DC 20059 USA
8.Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA
9.Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA
10.Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA
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Shao, Lisha,Lu, Binyan,Wen, Zhexing,et al. Disrupted-in-Schizophrenia-1 (DISC1) protein disturbs neural function in multiple disease-risk pathways[J]. HUMAN MOLECULAR GENETICS,2017,26(14):2634-2648.
APA Shao, Lisha.,Lu, Binyan.,Wen, Zhexing.,Teng, Shaolei.,Wang, Lingling.,...&Zhong, Yi.(2017).Disrupted-in-Schizophrenia-1 (DISC1) protein disturbs neural function in multiple disease-risk pathways.HUMAN MOLECULAR GENETICS,26(14),2634-2648.
MLA Shao, Lisha,et al."Disrupted-in-Schizophrenia-1 (DISC1) protein disturbs neural function in multiple disease-risk pathways".HUMAN MOLECULAR GENETICS 26.14(2017):2634-2648.
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