Disrupted-in-Schizophrenia-1 (DISC1) protein disturbs neural function in multiple disease-risk pathways

Shao, L., Lu, B., Wen, Z., Teng, S., Wang, L., Zhao, Y., Wang, L., Ishizuka, K., Xu, X., Sawa, A., Song, H., Ming, G., Zhong, Y. (July 2017) Disrupted-in-Schizophrenia-1 (DISC1) protein disturbs neural function in multiple disease-risk pathways. Hum Mol Genet, 26 (14). pp. 2634-2648. ISSN 0964-6906

URL: https://www.ncbi.nlm.nih.gov/pubmed/28472294
DOI: 10.1093/hmg/ddx147


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 Drosophila model to dissect 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.

Item Type: Paper
Subjects: diseases & disorders > mental disorders > schizophrenia
organs, tissues, organelles, cell types and functions > tissues types and functions > neural networks
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > DISC1
CSHL Authors:
Communities: CSHL labs > Zhong lab
Depositing User: Matt Covey
Date: 15 July 2017
Date Deposited: 11 May 2017 16:30
Last Modified: 07 Jul 2021 14:02
PMCID: PMC5886174
Related URLs:
URI: https://repository.cshl.edu/id/eprint/34734

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