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Neuropharmacology. 2012 Mar;62(3):1230-41. doi: 10.1016/j.neuropharm.2010.12.027. Epub 2010 Dec 31.

DISC1-binding proteins in neural development, signalling and schizophrenia.

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Medical Genetics Section, Molecular Medicine Centre, Institute of Genetics & Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, Midlothian EH4 2XU, UK.


In the decade since Disrupted in Schizophrenia 1 (DISC1) was first identified it has become one of the most convincing risk genes for major mental illness. As a multi-functional scaffold protein, DISC1 has multiple identified protein interaction partners that highlight pathologically relevant molecular pathways with potential for pharmaceutical intervention. Amongst these are proteins involved in neuronal migration (e.g. APP, Dixdc1, LIS1, NDE1, NDEL1), neural progenitor proliferation (GSK3β), neurosignalling (Girdin, GSK3β, PDE4) and synaptic function (Kal7, TNIK). Furthermore, emerging evidence of genetic association (NDEL1, PCM1, PDE4B) and copy number variation (NDE1) implicate several DISC1-binding partners as risk factors for schizophrenia in their own right. Thus, a picture begins to emerge of DISC1 as a key hub for multiple critical developmental pathways within the brain, disruption of which can lead to a variety of psychiatric illness phenotypes.

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