P4HB and Alzheimer disease: Additionally, protein disulfide isomerase (PDI), an enzyme that catalyzes thiol–disulphide exchange, has been reported to be S-nitrosylated in AD brains, which might lead to alterations in its ability to facilitate disulfide bond formation and rearrangement reactions, consequently leading to increased accumulation of polyubiquitinylated proteins and activation of the ER-resident unfolded protein response (UPR) [151].