New work in mice indicates that defective function of the molecular ‘scaffold’ protein Disc1 results in behaviors resembling human schizophrenia and depression. Current treatments for these devastating diseases are palliative but not curative.
Prior work hints at a link between Disc1 and psychiatric illness. Some mood disorders in humans are ameliorated by drugs suppressing the function of PDE4B: a protein that binds to molecular scaffolds including Disc1 and metabolizes cAMP, a compound essential for transmission of cellular signals. From studies in humans, scientists are also aware of associations between Disc1 mutations and the incidence of psychiatric illnesses. However, whether these mutations altered Disc1 function, and thus whether Disc1 dysfunction actually contributed to brain pathology, was not determined.
An international group led by Yoichi Gondo, a scientist at RIKEN Genomic Sciences Center in Yokohama, used a mouse model to forge a causative link between alterations in Disc1 function and the pathology of psychiatric disorders. This work was published in a recent issue of Neuron1.