Protein Disulphide Isomerases: emerging roles of PDI and ERp57 in the nervous system and as therapeutic targets for ALS

摘要

Introduction: There is increasing evidence that endoplasmic reticulum (ER) chaperones Protein Disulphide Isomerase (PDI) and ERp57 (endoplasmic reticulum protein 57) are protective against neurodegenerative diseases related to protein misfolding, including Amyotrophic Lateral Sclerosis (ALS). PDI and ERp57 also possess disulphide interchange activity, in which protein disulphide bonds are oxidized, reduced and isomerized, to form their native conformation. Recently, missense and intronic variants of PDI and ERp57 were associated with ALS, implying that PDI proteins are relevant to ALS pathology.