How has DISC1 enabled drug discovery?
Growing genetic and clinical evidence has shown that disrupted-in-schizophrenia 1 (DISC1) is one of the most compelling risk genes for schizophrenia and other major mental disorders. The understanding of the role that DISC1 plays in neuronal development and cell signaling has been greatly enhanced by the identification of DISC1 binding partners, an appreciation of its expression during development and functional studies using RNA interference. But what is the impact of this explosion of data for psychiatric drug discovery? Though we are at a very early stage of our understanding of DISC1 biology, it is an important time to review what has already been achieved and to discuss its impact. DISC1 biology has enabled the identification of new therapeutic targets in the form of DISC1 binding partners and other molecules found within a large DISC1 interaction network, the so-called 'DISC1 interactome'. We will review the better characterized of these interactions and also emphasize the richness of potential targets in the more poorly studied areas of the interactome. Furthermore, DISC1 has encouraged the development of new animal models for psychiatric disorders, which is critical for the study of disease biology. Thus, DISC1 may have the potential to not only point us in the direction of novel drug targets but also provide more relevant animal models for compound testing.
Wang
Qi
Q
Discovery Neuroscience, Wyeth Research, Princeton, NJ, USA.
Jaaro-Peled
Hanna
H
Sawa
Akira
A
Brandon
Nicholas J
NJ
D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015195:Drug Design; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019965:Neurocognitive Disorders / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics
D002352:Carrier Proteins; C412476:DISC1 protein, human; C421108:NDEL1 protein, human; D009419:Nerve Tissue Proteins; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4