The Role of the NADPH Oxidase NOX2 in Prion Pathogenesis

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The deposition of misfolded, aggregated prion protein in the brain causes transmissible spongiform encephalopathies (TSE), a group of disorders including Creutzfeldt–Jakob disease and mad cow disease. TSE are characterized by neurodegeneration and progressive, lethal neurological dysfunction. Signs of oxidative damage are found in TSE, implying excessive production of reactive oxygen species (ROS), yet their source is unclear. Here, we analyzed the role of the NADPH oxidase enzyme, NOX2, in prion pathogenesis. NOX2 is a membrane-bound electrochemical pump that generates ROS. We found that NOX2 is upregulated in the brains of patients with Creutzfeldt-Jakob disease and of prion-infected mice. Interestingly, NOX2 ablation led to abrogation of ROS production in mice inoculated with prions, and was associated with a milder clinical course of the disease and increased life expectancy. We conclude that NOX2 is a relevant contributor to the excessive production of ROS. This study spawns the possibility that inhibiting NOX2 activation might help attenuate prion disease progression – a legitimate and important goal even if there is little reason to expect anti-NOX2 therapies to be curative.

Vyšlo v časopise: The Role of the NADPH Oxidase NOX2 in Prion Pathogenesis. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004531
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004531

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