Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic Approaches
Sanfilippo syndrome or mucopolysaccharidosis III is a lysosomal storage disorder caused by mutations in genes responsible for the degradation of heparan sulfate, a glycosaminoglycan located in the extracellular membrane. Undegraded heparan sulfate molecules accumulate within lysosomes leading to cel...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/21/7819 |
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| author | Noelia Benetó Lluïsa Vilageliu Daniel Grinberg Isaac Canals |
| author_facet | Noelia Benetó Lluïsa Vilageliu Daniel Grinberg Isaac Canals |
| author_sort | Noelia Benetó |
| collection | DOAJ |
| description | Sanfilippo syndrome or mucopolysaccharidosis III is a lysosomal storage disorder caused by mutations in genes responsible for the degradation of heparan sulfate, a glycosaminoglycan located in the extracellular membrane. Undegraded heparan sulfate molecules accumulate within lysosomes leading to cellular dysfunction and pathology in several organs, with severe central nervous system degeneration as the main phenotypical feature. The exact molecular and cellular mechanisms by which impaired degradation and storage lead to cellular dysfunction and neuronal degeneration are still not fully understood. Here, we compile the knowledge on this issue and review all available animal and cellular models that can be used to contribute to increase our understanding of Sanfilippo syndrome disease mechanisms. Moreover, we provide an update in advances regarding the different and most successful therapeutic approaches that are currently under study to treat Sanfilippo syndrome patients and discuss the potential of new tools such as induced pluripotent stem cells to be used for disease modeling and therapy development. |
| first_indexed | 2024-03-10T15:25:43Z |
| format | Article |
| id | doaj.art-7ea88774fc504aed961b083d4b574344 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:25:43Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7ea88774fc504aed961b083d4b5743442023-11-20T18:04:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121781910.3390/ijms21217819Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic ApproachesNoelia Benetó0Lluïsa Vilageliu1Daniel Grinberg2Isaac Canals3Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, CIBERER, IBUB, IRSJD, E-08028 Barcelona, SpainDepartment of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, CIBERER, IBUB, IRSJD, E-08028 Barcelona, SpainDepartment of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, CIBERER, IBUB, IRSJD, E-08028 Barcelona, SpainStem Cells, Aging and Neurodegeneration Group, Department of Clinical Sciences, Neurology, Lund Stem Cell Center, Lund University, SE-22184 Lund, SwedenSanfilippo syndrome or mucopolysaccharidosis III is a lysosomal storage disorder caused by mutations in genes responsible for the degradation of heparan sulfate, a glycosaminoglycan located in the extracellular membrane. Undegraded heparan sulfate molecules accumulate within lysosomes leading to cellular dysfunction and pathology in several organs, with severe central nervous system degeneration as the main phenotypical feature. The exact molecular and cellular mechanisms by which impaired degradation and storage lead to cellular dysfunction and neuronal degeneration are still not fully understood. Here, we compile the knowledge on this issue and review all available animal and cellular models that can be used to contribute to increase our understanding of Sanfilippo syndrome disease mechanisms. Moreover, we provide an update in advances regarding the different and most successful therapeutic approaches that are currently under study to treat Sanfilippo syndrome patients and discuss the potential of new tools such as induced pluripotent stem cells to be used for disease modeling and therapy development.https://www.mdpi.com/1422-0067/21/21/7819Sanfilippo syndromemucopolysaccharidosis IIIlysosomal storage disordersheparan sulfateanimal modelsinduced pluripotent stem cells |
| spellingShingle | Noelia Benetó Lluïsa Vilageliu Daniel Grinberg Isaac Canals Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic Approaches International Journal of Molecular Sciences Sanfilippo syndrome mucopolysaccharidosis III lysosomal storage disorders heparan sulfate animal models induced pluripotent stem cells |
| title | Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic Approaches |
| title_full | Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic Approaches |
| title_fullStr | Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic Approaches |
| title_full_unstemmed | Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic Approaches |
| title_short | Sanfilippo Syndrome: Molecular Basis, Disease Models and Therapeutic Approaches |
| title_sort | sanfilippo syndrome molecular basis disease models and therapeutic approaches |
| topic | Sanfilippo syndrome mucopolysaccharidosis III lysosomal storage disorders heparan sulfate animal models induced pluripotent stem cells |
| url | https://www.mdpi.com/1422-0067/21/21/7819 |
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