Role of DISC1 in Neuronal Trafficking and its Implication in Neuropsychiatric Manifestation and Neurotherapeutics
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Disrupted-in-schizophrenia 1 (DISC1) was initially identified as a gene disrupted by a translocation mutation co-segregating with a variety of psychotic and mood disorders in a Scottish pedigree. In agreement with this original finding, mouse models that perturb Disc1 display deficits of behaviors in specific dimensions, such as cognition and emotion, but not a motor dimension. Although DISC1 is not a risk gene for sporadic cases of specific psychiatric disorders defined by categorical diagnostic criteria (e.g., schizophrenia and major depressive disorder), DISC1 is now regarded as an important molecular lead to decipher molecular pathology for specific dimensions relevant to major mental illnesses. Emerging evidence points to the role of DISC1 in the regulation of intracellular trafficking of a wide range of neuronal cargoes. We will review recent progress in this aspect of DISC1 biology and discuss how we could utilize this body of knowledge to better understand the pathophysiology of mental illnesses.
KeywordsDISC1 Trafficking Interactome Cargo Schizophrenia
We thank Dr. Akira Sawa (Johns Hopkins University) for advice. This work was supported by grants from DOD/CDMRP (W81XWH-11-1-0269) and CTF-DDI (TT), Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (15H04275, 16H06568 and 16 K14579 to TH; 15H01285 and 16 K01948 to TS), Takeda Science Foundation (TH), the Naito Foundation (TH), and the Kato Memorial Trust for Nambyo Research (TH). This work was performed, in part, under the International Cooperative Research Program of Institute for Protein Research, Osaka University, ICRa-17-13. The authors declare no conflict of interest.
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