期刊
EXPERIMENTAL CELL RESEARCH
卷 407, 期 1, 页码 -出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2021.112785
关键词
Mucopolysaccharidosis type IIIB; Sanfilippo syndrome B; Lysosomal storage disease; iPSC disease model; delta-tocopherol; 2-Hydroxypropyl-b-cyclodextrin
资金
- Intramural Research Program of the National Center for Advancing Translational Sciences, NIH
MPS IIIB is a lysosomal disease caused by mutations in the NAGLU gene, with no effective treatment currently available. The study showed that MPS IIIB neural stem cells and neurons can serve as a disease model system for evaluating drug efficacy and compound screening for drug development.
Mucopolysaccharidosis type IIIB (MPS IIIB) is a lysosomal disease caused by mutations in the NAGLU gene encoding alpha-N-acetylglucosaminidase (NAGLU) which degrades heparan sulfate in lysosomes. Deficiency in NAGLU results in lysosomal accumulation of glycosaminoglycans (GAGs) and neurological symptoms. Currently, there is no effective treatment or cure for this disease. In this study, induced pluripotent stem cell lines were established from two MPS IIIB patient fibroblast lines and differentiated into neural stem cells and neurons. MPS IIIB neural stem cells exhibited NAGLU deficiency accompanied with GAG accumulation, as well as lysosomal enlargement and secondary lipid accumulation. Treatments with recombinant NAGLU, delta-tocopherol, and 2-hydroxypropyl-b-cyclodextrin significantly reduced the disease phenotypes in these cells. These results indicate the MPS IIIB neural stem cells and neurons have the disease relevant phenotype and can be used as a cell-based disease model system for evaluation of drug efficacy and compound screening for drug development.
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