دورية أكاديمية
ERp57 is protective against mutant SOD1-induced cellular pathology in amyotrophic lateral sclerosis.
| العنوان: | ERp57 is protective against mutant SOD1-induced cellular pathology in amyotrophic lateral sclerosis. |
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| المؤلفون: | Parakh S; Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia., Jagaraj CJ; Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia., Vidal M; Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia., Ragagnin AMG; Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia., Perri ER; Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia., Konopka A; Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia., Toth RP; Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia., Galper J; Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia., Blair IP; Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia., Thomas CJ; Department of Physiology, Anatomy and Microbiology, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia., Walker AK; Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia., Yang S; Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia., Spencer DM; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia., Atkin JD; Centre for MND Research, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC 3086, Australia. |
| المصدر: | Human molecular genetics [Hum Mol Genet] 2018 Apr 15; Vol. 27 (8), pp. 1311-1331. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: IRL Press at Oxford University Press Country of Publication: England NLM ID: 9208958 Publication Model: Print Cited Medium: Internet ISSN: 1460-2083 (Electronic) Linking ISSN: 09646906 NLM ISO Abbreviation: Hum Mol Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, England ; New York : IRL Press at Oxford University Press, c1992- |
| مواضيع طبية MeSH: | Amyotrophic Lateral Sclerosis/*genetics , DNA-Binding Proteins/*genetics , Endoplasmic Reticulum Stress/*genetics , Neurons/*metabolism , Protein Disulfide-Isomerases/*genetics , Superoxide Dismutase-1/*genetics, Aged ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/pathology ; Animals ; Apoptosis ; Cell Line ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/metabolism ; Embryo, Mammalian ; Female ; Gene Expression Regulation ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Mutation ; Neurons/pathology ; Primary Cell Culture ; Protein Disulfide-Isomerases/antagonists & inhibitors ; Protein Disulfide-Isomerases/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Signal Transduction ; Spinal Cord/metabolism ; Spinal Cord/pathology ; Superoxide Dismutase-1/metabolism |
| مستخلص: | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder and mutations in superoxide dismutase 1 (SOD1) account for 20% of familial ALS cases. The aetiology of ALS remains unclear, but protein misfolding, endoplasmic reticulum (ER) stress and neuronal apoptosis are implicated. We previously established that protein disulphide isomerase (PDIA1) is protective against ER stress and apoptosis in neuronal cells expressing mutant SOD1, and recently mutations in PDIA1 and related PDI family member endoplasmic reticulum protein 57 (ERp57/PDIA3), were associated with ALS. Here, we examined whether ERp57 is also protective against mutant SOD1 or whether distinct specificity exists amongst individual PDI family members. Neuronal cells co-expressing SOD1 and ERp57 were examined for inclusion formation, ER stress, ubiquitin proteasome system (UPS) dysfunction and apoptosis. Over-expression of ERp57 inhibited inclusion formation, ER stress, UPS dysfunction and apoptosis, whereas silencing of ERp57 expression enhanced mutant SOD1 inclusion formation, ER stress and toxicity, indicating a protective role for ERp57 against SOD1 misfolding. ERp57 also inhibited the formation of mutant SOD1 inclusions and apoptosis in primary cortical neurons, thus confirming results obtained from cell lines. ERp57 partially co-localized with TAR DNA-binding protein-43 (TDP-43)-positive inclusions in spinal cords from sporadic ALS patients, thus linking ERp57 to protein misfolding in human sporadic disease. Our results therefore imply that ERp57 has a protective role against pathological events induced by mutant SOD1 and they link ERp57 to the misfolding of TDP-43. This study therefore has implications for the design of novel therapeutics based on the activities of the PDI family of proteins. |
| المشرفين على المادة: | 0 (DNA-Binding Proteins) 0 (RNA, Small Interfering) 0 (SOD1 protein, human) 0 (TARDBP protein, human) EC 1.15.1.1 (Superoxide Dismutase-1) EC 5.3.4.1 (Protein Disulfide-Isomerases) EC 5.3.4.1. (PDIA3 protein, human) |
| تواريخ الأحداث: | Date Created: 20180207 Date Completed: 20190208 Latest Revision: 20201109 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1093/hmg/ddy041 |
| PMID: | 29409023 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1460-2083 |
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| DOI: | 10.1093/hmg/ddy041 |