TABLE 1.

Role of Protein Disulfide Isomerases in neurodegenerative diseases.

Disease	Effect	Reference
PrDs	• ERp57 and PDIA1 are upregulated in post mortem brain samples of CJD patients.• ERp57 levels correlate with disease progression in murine scrapie models.• ERp57 and PDIA1 expression protect against PrPSc toxicity in vitro.• PDIA1 is nitrosylated in PrDs models.• Inhibition of PDI activity reduces PrPSc replication in vitro.	10,20,22
AD	• PDIA1 inhibits Tau aggregation.• Pharmacological activation of ERp57 reduces clinical hallmarks of AD in mouse models.• ERp57 physically interacts with amyloid-β and prevents its aggregation.• Inhibition of ERp57 and PDIA1 protects against amyloid-β toxicity.	20,27,33
PD	• PDIA1 is upregulated in many toxicological models of PD.• PDIA1 is S-nitrosylated in brain tissue of PD patients.	20
ALS	• ERp57 and PDIA1 mutations are risk factors to develop ALS.• PDIA1 and ERp57 are upregulated in mouse models and post mortem tissue and CSF.• Upregulation of ERp57 in blood of patients is a possible biomarker of the disease• PDIA1 reduces mutant SOD1 aggregation in vitro.• PDIA1 co-localizes with SOD1, FUS and TDP-43 inclusion in ALS-derived tissue.	20,29,31,32
HD	• Inhibition of ERp57 or PDIA1 suppresses neuronal degeneration induced by mutant Huntingtin in vitro.	20

A summary of selected literature related to protein disulfide isomerases in protein misfolding disorders (PMDs). Abbreviations used: PrDs, Prion related Disorders; AD, Alzheimer disease; PD, Parkinson disease; ALS, Amyotrophic Lateral Sclerosis; HD, Hungtington's disease. Most primary references can be found in.²⁰