Abstract
Psychiatric disorders (such as bipolar disorder, depression, and schizophrenia) affect the lives of millions of individuals worldwide. Despite the tremendous efforts devoted to various types of psychiatric studies and rapidly accumulating genetic information, the molecular mechanisms underlying psychiatric disorder development remain elusive. Among the genes that have been implicated in schizophrenia and other mental disorders, disrupted in schizophrenia 1 (DISC1) and glycogen synthase kinase 3 (GSK3) have been intensively investigated. DISC1 binds directly to GSK3 and modulates many cellular functions by negatively inhibiting GSK3 activity. The human DISC1 gene is located on chromosome 1 and is highly associated with schizophrenia and other mental disorders. A recent study demonstrated that a neighboring gene of DISC1, translin-associated factor X (TRAX), binds to the DISC1/GSK3β complex and at least partly mediates the actions of the DISC1/GSK3β complex. Previous studies also demonstrate that TRAX and most of its interacting proteins that have been identified so far are risk genes and/or markers of mental 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.
Highlights
Mental disorders have recently become great concerns because of the resultant heavy social and economic burdens on societies [1,2,3]
Because the incomplete repair of oxidative DNA damage may contribute to the development of psychotic disorders [1, 17, 18] and because translin-associated factor X (TRAX) and many of its interacting proteins (Table 1) are risk genes and/or markers of mental disorders, the present review focuses on the emerging role of TRAX/disrupted in schizophrenia 1 (DISC1) interactome(s) in DNA repair as well as their potential implications in psychiatric disorders
Because the studies regarding TRAX are still in their infancy, the overlapping functional pathways of DISC1 and TRAX appear limited at this time (Table 2) but may become more evident when more binding partners of TRAX are revealed in the future
Summary
Mental disorders (such as bipolar disorder, depression, and schizophrenia) have recently become great concerns because of the resultant heavy social and economic burdens on societies [1,2,3].
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