DISCopathies: brain disorders related to DISC1 dysfunction

During the last decade, disrupted-in-schizophrenia 1 (DISC1) has emerged as a protein involved in the pathogenesis of chronic mental diseases such as schizophrenia, or recurrent affective disorders. Its multiple functions include regulating corticogenesis, synapse integrity and adult neurogenesis, indicating a key role in the hard-wiring and the maintenance of communicative abilities of the brain. From its cellular functions, the DISC1 protein is a 'molecular facilitator', which interacts with a quartenary complex including NDEL1, NDE1, LIS1, as well as the signaling molecules, GSK-3beta, PDE4B, and others. DISC1 oligomerizes, can form misassembled dysfunctional multimers as well as disease-associated insoluble protein complexes which qualify these diseases as protein conformational disorders. Disease categories ultimately serve the goal of defining pathophysiological conditions amenable to similar and efficient (pharmaco) therapies. Here, it is proposed to classify brain disorders related to dysfunctional DISC1 protein as one disease entity, that is, as DISCopathies.