Methionine oxidation within the prion protein.

Prion diseases are characterized by the self-templated misfolding of the cellular prion protein (PrP) into infectious aggregates (PrP). The detailed molecular basis of the misfolding and aggregation of PrP remains incompletely understood. It is believed that the transient misfolding of PrP into partially structured intermediates precedes the formation of insoluble protein aggregates and is a critical component of the prion misfolding pathway. A number of environmental factors have been shown to induce the destabilization of PrP and promote its initial misfolding. Recently, oxidative stress and reactive oxygen species (ROS) have emerged as one possible mechanism by which the destabilization of PrP can be induced under physiological conditions. Methionine residues are uniquely vulnerable to oxidation by ROS and the formation of methionine sulfoxides leads to the misfolding and subsequent aggregation of PrP. Here, we provide a review of the evidence for the oxidation of methionine residues in PrP and its potential role in the formation of pathogenic prion aggregates.