We show (i) that PfGrx-catalyzed redox reactions outcompete uncatalyzed reactions between roGFP2 and GSH or GSSG by several orders of magnitude, (ii) that the PfGrx-catalyzed reduction and oxidation of roGFP2 occur via a mono- and not a dithiol mechanism, and (iii) that the reduction of roGFP2(S 2 ) as a model non-glutathione disulfide substrate most likely involves a rate-limiting glutathionylation in a ternary complex with a GSH molecule that is activated at the 1st glutathione-interaction site of PfGrx
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This is complicated because as a polar, charged tripeptide, transport of GSH is significantly inhibited by the blood-brain barrier (BBB), thus limiting effective delivery to brain-resident immune cells such as microglia which are central drivers of neuroinflammatory pathology (Valdovinos-Flores and Gonsebatt, 2012
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