Journal
JOURNAL OF THE NEUROLOGICAL SCIENCES
Volume 385, Issue -, Pages 49-56Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jns.2017.12.010
Keywords
Marinesco-Sjogren syndrome; ER stress; Lymphoblastoid cell line; Tunicamycin; Apoptosis; Tauroursodeoxycholic acid
Categories
Funding
- Japan Agency for Medical Research and Development (AMED) [15652552]
- Research on Measures for Intractable Diseases grant from the Ministry of Health, Labour, and Welfare [H22-128]
Ask authors/readers for more resources
Background and objective: Marinesco-Sjogren syndrome (MSS) is an autosomal recessive infantile-onset disorder characterized by cataracts, cerebellar ataxia, and progressive myopathy caused by mutation of SILL. In mice, a defect in SIL1 causes endoplasmic reticulum (ER) chaperone dysfunction, leading to unfolded protein accumulation and increased ER stress. However, ER stress and the unfolded protein response (UPR) have not been investigated in MSS patient-derived cells. Methods: Lymphoblastoid cell lines (LCLs) were established from four MSS patients. Spontaneous and tunicamycin-induced ER stress and the UPR were investigated in MSS-LCLs. Expression of UPR markers was analyzed by western blotting. ER stress-induced apoptosis was analyzed by flow cytometry. The cytoprotective effects of ER stress modulators were also examined. Results: MSS-LCLs exhibited increased spontaneous ER stress and were highly susceptible to ER stress-induced apoptosis. The inositol-requiring protein la (IRE1 alpha)-X-box-binding protein 1 (XBP1) pathway was mainly up regulated in MSS-LCLs. Tauroursodeoxycholic acid (TUDCA) attenuated ER stress-induced apoptosis. Conclusion: MSS patient-derived cells exhibit increased ER stress, an activated UPR, and susceptibility to ER stress-induced death. TUDCA reduces ER stress-induced death of MSS patient-derived cells. The potential of TUDCA as a therapeutic agent for MSS could be explored further in preclinical studies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available