title: Molecular basis of major psychiatric diseases such as schizophrenia and depression.
abstract: 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. DISC1 is involved in neural development directly via adhesion molecules or via its binding partners of DISC1 such as elongation protein ζ-1 (FEZ1), DISC1-binding zinc-finger protein (DBZ) and kendrin. PACAP also regulates neural development via stathmin 1 or via regulation of the DISC1-DBZ binding. Dysbindin is also involved in neural development by regulating centrosomal microtubule network formation. All such molecules examined to date are involved in neural development. Thus, these findings provide new molecular insights into the mechanisms of neural development and neuropsychiatric disorders. On the other hand, in addition to neurons, both DISC and DBZ have been detected in oligodendrocytes and implicated in regulating oligodendrocyte differentiation. DISC1 inhibits the differentiation of oligodendrocyte precursor cells into oligodendrocytes, while DBZ has a positive regulatory role in oligodendrocyte differentiation. Evidence suggesting that disturbance of oligodendrocyte development causes major depression is also described.
authors.affiliation: Osaka Prefectural Hospital Organization, Osaka, 558-8558, Japan, m.tohyama@opho.jp.
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyata
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hattori
authors.forename: Shoko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Matsuzaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D002148:Calmodulin-Binding Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology; D003863:Depression / Q000235:genetics*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins / Q000235:genetics* / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics; D009836:Oligodendroglia / Q000166:cytology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics* / Q000502:physiology; D011485:Protein Binding; D012559:Schizophrenia / Q000235:genetics*; D050777:Stathmin / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
chemical_list: C495401:ADCYAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002148:Calmodulin-Binding Proteins; C412476:DISC1 protein, human; D004268:DNA-Binding Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; C528597:FEZ1 protein, human; D009419:Nerve Tissue Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C493995:STMN1 protein, human; D050777:Stathmin; D014157:Transcription Factors; C475725:ZNF365 protein, human; C410004:kendrin