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Role of DISC1 in neural development and schizophrenia

Journal

CURRENT OPINION IN NEUROBIOLOGY
Volume 17, Issue 1, Pages 95-102

Publisher

CURRENT BIOLOGY LTD
DOI: 10.1016/j.conb.2007.01.007

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Funding

  1. Medical Research Council [G0600214, G0100266] Funding Source: Medline
  2. MRC [G0600214, G0100266] Funding Source: UKRI
  3. Medical Research Council [G0100266, G0600214] Funding Source: researchfish

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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.

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