Research ArticleNeuroscience

The Protease Omi Cleaves the Mitogen-Activated Protein Kinase Kinase MEK1 to Inhibit Microglial Activation

Science Signaling  21 Aug 2012:
Vol. 5, Issue 238, pp. ra61
DOI: 10.1126/scisignal.2002946

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Omi Inhibits Neuroinflammation

Progression of the neurodegenerative disorder Parkinson’s disease is associated with the activation of microglia, the resident macrophages of the central nervous system, and the production of proinflammatory molecules. Mutations in the gene encoding the protease Omi that inhibit its protease activity are associated with Parkinson’s disease, but the mechanism involved is unclear. Hu et al. showed that microglia from mice expressing a protease-deficient mutant Omi had increased activation of the kinases ERK1 and ERK2 and of the transcription factor NF-κB than did microglia from wild-type mice, and this increased signaling resulted in the enhanced production of proinflammatory factors. In vitro studies showed that Omi cleaved the kinase MEK1, which is upstream of the ERKs, and thus limited ERK activation. Together, these data suggest that Omi acts as an endogenous inhibitor of ERK signaling and inflammation in microglia.