Protein Disulfide Isomerase Immunopositive Glial Cytoplasmic Inclusions in Patients With Multiple System Atrophy

ABSTRACTBackground: Glial cytoplasmic inclusions (GCIs) are the pathological hallmarks of multiple system atrophy (MSA) and α-synuclein is abnormally deposited in GCIs. Protein disulfide isomerase (PDI) is a member of the thioredoxin superfamily and is believed to accelerate the folding of disulfide-bonded proteins by catalyzing the disulfide interchange reaction, which is the rate-limiting step during protein folding in the luminal space of the endoplasmic reticulum (ER). Nitric-oxide-induced (NO-induced) S-nitrosylation of PDI inhibits its enzymatic activity, leading to the accumulation of polyubiquitinated proteins, and activates the unfolded protein response in neurodegenerative diseases. Materials and Methods: Postmortem brain specimens from five patients with MSA and five normal control brains were utilized in this immunohistochemical study. Results: We found GCIs positive for anti-PDI antibody in the brain of patients with MSA. In addition, we observed colocalization of α-synuclein and leucine-rich...