Peer-reviewed veterinary case report
Protein disulphide isomerase linked to mutant SOD1 in dog
By Chang, Rachel C et al.·Published in Neuroreport·2019·Veterinary Science of the University of Melbourne., Australia·View original on PubMed →
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Original publication title: Protein disulphide isomerase is associated with mutant SOD1 in canine degenerative myelopathy.
- Species:
- dog
Plain-English summary
A study found that dogs with degenerative myelopathy (DM), a serious nerve disease, showed signs of stress in their spinal cord cells due to a mutation in the SOD1 gene. This stress is similar to what is seen in humans with amyotrophic lateral sclerosis (ALS). Researchers discovered that a protein called protein disulphide isomerase (PDI) was increased in these dogs and seemed to work alongside the misfolded SOD1 protein. This suggests that PDI might help protect against the damage caused by SOD1 misfolding, and it raises the possibility that targeting PDI could be a new way to treat DM in dogs.
People also search for: dog degenerative myelopathy treatment · SOD1 mutation in dogs · canine ALS symptoms · PDI protein in dogs · dog spinal cord disease
Abstract
Canine degenerative myelopathy (DM) is a fatal neurodegenerative disorder prevalent in the canine population. It may represent a unique, naturally occurring disease model for human amyotrophic lateral sclerosis (ALS) because of similar clinical signs and association with superoxide dismutase 1 gene (SOD1) mutations. Misfolded SOD1 aggregates and endoplasmic reticulum (ER) stress are major pathophysiological features associated with ALS. Interestingly, an ER foldase, protein disulphide isomerase (PDI) is upregulated during ALS and it co-localizes with SOD1 inclusions in ALS patient tissues. Furthermore, mutations in the gene encoding PDI were recently associated with ALS. Given the genetic similarity between DM and ALS, we investigated whether ER stress and PDI were associated with DM. Protein extracts from spinal cord tissue of DM-affected dogs bearing a SOD1 mutation were examined for ER stress by western blotting. Immunohistochemical staining was also carried out to examine co-localization between endogenous PDI and SOD1 inclusions in spinal cord tissues of dogs affected with DM. PDI and CHOP, the proapoptotic protein induced during ER stress, were significantly upregulated in DM-affected dogs compared with controls. Furthermore, PDI co-localized with intracellular SOD1 aggregates in DM-affected dogs in all motor neurons examined, indicating that PDI may be a cellular defence mechanism against SOD1 misfolding in DM. Our results imply that ER stress is induced in DM-affected dogs; hence, it is a common pathological mechanism associated with both ALS and DM. The possibility that PDI may be a therapeutic target to inhibit SOD1 aggregation in DM dogs is also raised by this study.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/30422940/