Alzheimers disease (AD), the most common form of dementia worldwide 270,271 , is characterized at the molecular level by the accumulation of A plaques, tau neurofibrillary tangles (NFTs), declined NAD + levels, mitochondrial stress, and impaired mitophagy, occurring first in the medial temporal lobe and eventually spreading to temporal and parietal cortices, and cortex 112,242,243,270,271,272
Wang W-L, Chen K-H, Pan Y-C, Yang S-N, Chan Y-Y
Dysfunction or disruption of the redox buffer has been implicated in various diseases and the implications make GSH, GSSG, and their related systems valid and effective targets for medicinal chemistry interventions
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