[Schizophrenia, neurodevelopment and glycogen synthase kinase-3].
The Neurodevelopmental Hypothesis of the etiology of schizophrenia suggests that interaction between genetic and environmental events occurring during critical early periods in neuronal growth may negatively influence the way by which nerve cells are laid down, differentiated and selectively culled by apoptosis. Recent advances toward understanding the regulation of brain development offer insights into possible mechanisms of developmental brain changes. One such factor is the Wnt family of genes, which plays a central role in normal brain development. Activation of the Wnt cascade leads to inactivation of glycogen synthase kinase-3 beta (GSK-3 beta), accumulation and activation of beta-catenin and expression of genes involved in neuronal development. It has been proposed that alteration in the transduction cascade of the Wnt signaling pathway represents an aberrant neurodevelopment in schizophrenia. The role of GSK-3 in developmental brain changes in schizophrenia may not be restricted to the Wnt signaling cascade. GSK-3 alpha, reported to be 80% lower in lymphocytes of schizophrenic patients is a regulatory enzyme of some neuronal proteins implicated to be aberrant in schizophrenia. Programmed cell death is an essential component of normal brain development. Spatial or temporal errors in the stimuli that initiate this pathway or processes within it can result in pathological neuronal development. Increased density of neuronal population in the cortical subplate, found in postmortem brains of schizophrenic patients may imply reduced programmed cell death. The possible role of GSK-3 beta, a pro-apoptotic factor participating in signal transduction involved in cell survival, is discussed in relation to schizophrenia.
D001921:Brain / Q000201:enzymology / Q000254:growth & development / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D009420:Nervous System / Q000254:growth & development*; D009474:Neurons / Q000473:pathology; D012559:Schizophrenia / Q000201:enzymology* / Q000473:pathology; D015398:Signal Transduction
D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha