title: Protein Disulphide Isomerases: emerging roles of PDI and ERp57 in the nervous system and as therapeutic targets for ALS.
abstract: 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. Areas covered: Here, we discuss possible implications of the PDI and ERp57 variants, as well as recent studies describing previously unrecognized roles for PDI and ERp57 in the nervous system. Therapeutics based on PDI may therefore be attractive candidates for ALS. However, in addition to its protective functions, aberrant, toxic roles for PDI have recently been described. These functions need to be fully characterized before effective therapeutic strategies can be designed. Expert opinion: These disease-associated variants of PDI and ERp57 provide additional evidence for an important role for PDI proteins in ALS. However, there are many questions remaining unanswered that need to be addressed before the potential of the PDI family in relation to ALS can be fully realized.
authors: a Department of Biomedical Sciences, Faculty of Medicine and Health Sciences , Macquarie University , Sydney , Australia.
authors: Emma
authors: E
authors: Perri
authors: a Department of Biomedical Sciences, Faculty of Medicine and Health Sciences , Macquarie University , Sydney , Australia.
authors: Sonam
authors: S
authors: Parakh
authors: a Department of Biomedical Sciences, Faculty of Medicine and Health Sciences , Macquarie University , Sydney , Australia.|b Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science , La Trobe University , Melbourne , Australia.
authors: Julie
authors: J
authors: Atkin
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology* / Q000628:therapy; D000818:Animals; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D057165:Proteostasis Deficiencies / Q000503:physiopathology / Q000628:therapy
chemical_list: D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human
keywords: Amyotrophic Lateral Sclerosis (ALS); ER chaperones; ERp57 (endoplasmic reticulum protein 57); PDIA1; PDIA3; Protein Disulphide Isomerase (PDI); nervous system; neurodegeneration; therapeutics; variants