Key result
DISC1 disruption impairs critical brain developmental pathways and is linked to psychiatric illnesses including schizophrenia.
Why the study?
DISC1 is a key risk gene for major mental illness with multiple protein interaction partners implicating critical molecular pathways relevant to schizophrenia.
DISC1 is a multi-functional scaffold protein that interacts with multiple partners involved in neural development and signalling, highlighting its role as a risk gene for schizophrenia.
Does not support clinical DISC1 testing; leaves open targeted pathway modulation in schizophrenia.
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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Bradshaw et al. (2011) conducted a review in Schizophrenia. DISC1-binding proteins was evaluated. DISC1 acts as a key hub for multiple critical developmental pathways within the brain, disruption of which can lead to a variety of psychiatric illness phenotypes including schizophrenia.
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