DISC1 at 10: connecting psychiatric genetics and neuroscience.
Psychiatric genetics research, as exemplified by the DISC1 gene, aspires to inform on mental health etiology and to suggest improved strategies for intervention. DISC1 was discovered in 2000 through the molecular cloning of a chromosomal translocation that segregated with a spectrum of major mental illnesses in a single large Scottish family. Through in vitro experiments and mouse models, DISC1 has been firmly established as a genetic risk factor for a spectrum of psychiatric illness. As a consequence of its protein scaffold function, the DISC1 protein impacts on many aspects of brain function, including neurosignaling and neurodevelopment. DISC1 is a pathfinder for understanding psychopathology, brain development, signaling and circuitry. Although much remains to be learnt and understood, potential targets for drug development are starting to emerge, and in this review, we will discuss the 10 years of research that has helped us understand key roles of DISC1 in psychiatric disease.
Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK. david.porteous@ed.ac.uk
David J
DJ
Porteous
J Kirsty
JK
Millar
Nicholas J
NJ
Brandon
Akira
A
Sawa
D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D005826:Genetics, Medical; D006801:Humans; D001523:Mental Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009488:Neurosciences; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D015398:Signal Transduction / Q000235:genetics*; D014178:Translocation, Genetic
C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517360:PDE4B protein, human