Role of DISC1 in neural development and schizophrenia

S. Mackie, J. K. Millar, D. J. Porteous

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

How can we hope to explain mechanistically the schizophrenic phenotype? Perhaps through the reductionist approach of genetics, which is beginning to yield biological clues. Growing evidence supports the view that the well-established genetic risk factor DISC1 plays an important role in schizophrenia biology by interacting with FEZ1 and NDEL1 during neurodevelopment and with the phosphodiesterase PDE4B in neuronal cell signalling. Thus, DISC1 and its pathways support the neurodevelopmental hypothesis of schizophrenia and provide a mechanistic explanation for the characteristic cognitive deficits. Genetic variants of DISC1 also predispose to related affective (mood) disorders. As a consequence, we can speculate on the mechanisms of DISC1 action and possible routes to treatment for these common, debilitating brain disorders.
Original languageEnglish
Pages (from-to)95-102
Number of pages8
JournalCurrent Opinion in Neurobiology
Issue number1
Publication statusPublished - 2007

Keywords / Materials (for Non-textual outputs)

  • 3',5'-Cyclic-AMP Phosphodiesterases/genetics/metabolism Animals Brain/*embryology/*growth & development/metabolism Carrier Proteins/genetics/metabolism Cyclic Nucleotide Phosphodiesterases, Type 4 DNA-Binding Proteins/genetics/metabolism Gene Expression Regulation, Developmental/genetics Genetic Predisposition to Disease/*genetics Humans Models, Neurological Nerve Tissue Proteins/genetics/*metabolism Schizophrenia/genetics/metabolism/*physiopathology Tumor Suppressor Proteins/genetics/metabolism


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