Beschreibung:
<jats:title>Significance</jats:title>
<jats:p>We present evidence that alleviating nitrergic stress during early phases of neurodegeneration reduces neuroinflammatory posttranslational nitric oxide signaling and glycation-assisted dysfunction in the hippocampus of prion-diseased mice, a mechanism which might be applicable to other protein-misfolding neurodegenerative conditions. We confirmed that pharmacological suppression of nitrergic activity reduces the formation of advanced glycation end-products, diminishes prion protein misfolding, and averts neuronal dysfunction. This intervention could present an approach to diminish the detrimental neuroinflammatory effects seen in neurodegeneration and highlights nitrergic stress and glycation signaling as putative targets for disease-modifying treatments. The correlation between protein glycation and prion misfolding—as reported for several other misfolding proteins—links NO signaling to the neuroprotective effects seen following NOS inhibition.</jats:p>