Expression of proteins involved in the unfolded protein response (UPR) is altered in schizophrenia, according to new research. On the basis that protein processing and subcellular targeting are abnormal in schizophrenia, Pitna Kim and colleagues looked for dysregulation of the UPR, which normally maintains cellular homeostasis by preventing a build-up of unfolded or incorrectly folded proteins. The investigators measured levels of the initial stress sensors in the UPR and their downstream targets in the brains of people with schizophrenia and in controls. Levels of some initial sensors were altered, as were levels of some downstream targets. The findings indicate that dysregulation of the UPR and consequent alterations in protein processing contribute to the pathogenesis of schizophrenia.
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Kim, P. et al. Dysregulation of the unfolded protein response (UPR) in the dorsolateral prefrontal cortex in elderly patients with schizophrenia. Mol. Psychiatry https://doi.org/10.1038/s41380-019-0537-7 (2019)
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Fyfe, I. Protein processing dysfunction in schizophrenia. Nat Rev Neurol 15, 686 (2019). https://doi.org/10.1038/s41582-019-0278-x
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DOI: https://doi.org/10.1038/s41582-019-0278-x