We show levels of Disrupted-in-schizophrenia-1 (DISC1), which is genetically associated with psychiatric disorders and AD, decrease in the brains of AD patients and transgenic model mice and in Aβ-treated cultured cells.
This concept was underpinned by the function of the molecule disrupted-in-schizophrenia 1 (DISC1), which represents an intracellular hub of developmental processes and has been related to cognitive dysfunction in psychiatric disorders.
In the present review, we will focus on the emerging roles of TRAX and its interacting proteins (including DISC1 and GSK3β) in psychiatric disorders and the potential implications for developing therapeutic interventions.
A transgenic rat overexpressing non-mutant human DISC1, modeling aberrant proteostasis of the DISC1 protein, displays behavioral, biochemical and anatomical deficits consistent with aspects of mental disorders, including changes in the dorsal striatum, an anatomical region critical in the development of behavioral disorders.
Deficits in neurite outgrowth, possibly involving dysregulation of risk genes neuregulin-1 (NRG1) and disrupted in schizophrenia 1 (DISC1) have been implicated in psychiatric disorders including schizophrenia.
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.
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.
Our study uncovers a new mechanism of action for DISC1 based on its structure, and it has implications for how genetic insults may contribute to psychiatric disorders.
As disrupted-in-schizophrenia 1 (DISC1) is a genetic risk factor across a spectrum of psychiatric disorders, we focus on the results of studies using mice with various mutations of DISC1.
Recently several potential susceptibility genes for major psychiatric disorders (schizophrenia and major depression) such as disrupted-in-schizophrenia 1(DISC1), dysbindin and pituitary adenylate cyclase-activating polypeptide (PACAP) have been reported.
We previously reported that abnormalities of disrupted-in-Schizophrenia-1 (DISC1) and DISC1 binding zinc finger (DBZ) might cause major psychiatric disorders such as SZ.
Together, the results of this study suggest that the DISC1 translocation may increase the risk of psychiatric disorders in this pedigree by affecting neurostructural phenotypes such as cortical thickness.
Mutant DISC1 depletes wild-type DISC1 protein and, furthermore, dysregulates expression of many genes related to synapses and psychiatric disorders in human forebrain neurons.