Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses
Heparan sulfate (HS) is an essential glycosaminoglycan (GAG) as a component of proteoglycans, which are present on the cell surface and in the extracellular matrix. HS-containing proteoglycans not only function as structural constituents of the basal lamina but also play versatile roles in various p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/11724 |
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| author | Kohtaro Minami Hideto Morimoto Hiroki Morioka Atsushi Imakiire Masafumi Kinoshita Ryuji Yamamoto Tohru Hirato Hiroyuki Sonoda |
| author_facet | Kohtaro Minami Hideto Morimoto Hiroki Morioka Atsushi Imakiire Masafumi Kinoshita Ryuji Yamamoto Tohru Hirato Hiroyuki Sonoda |
| author_sort | Kohtaro Minami |
| collection | DOAJ |
| description | Heparan sulfate (HS) is an essential glycosaminoglycan (GAG) as a component of proteoglycans, which are present on the cell surface and in the extracellular matrix. HS-containing proteoglycans not only function as structural constituents of the basal lamina but also play versatile roles in various physiological processes, including cell signaling and organ development. Thus, inherited mutations of genes associated with the biosynthesis or degradation of HS can cause various diseases, particularly those involving the bones and central nervous system (CNS). Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders involving GAG accumulation throughout the body caused by a deficiency of GAG-degrading enzymes. GAGs are stored differently in different types of MPSs. Particularly, HS deposition is observed in patients with MPS types I, II, III, and VII, all which involve progressive neuropathy with multiple CNS system symptoms. While therapies are available for certain symptoms in some types of MPSs, significant unmet medical needs remain, such as neurocognitive impairment. This review presents recent knowledge on the pathophysiological roles of HS focusing on the pathogenesis of MPSs. We also discuss the possible use and significance of HS as a biomarker for disease severity and therapeutic response in MPSs. |
| first_indexed | 2024-03-09T21:38:06Z |
| format | Article |
| id | doaj.art-433defc4f6bd40d9836e9227031e7946 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:38:06Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-433defc4f6bd40d9836e9227031e79462023-11-23T20:38:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123191172410.3390/ijms231911724Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in MucopolysaccharidosesKohtaro Minami0Hideto Morimoto1Hiroki Morioka2Atsushi Imakiire3Masafumi Kinoshita4Ryuji Yamamoto5Tohru Hirato6Hiroyuki Sonoda7Research Division, JCR Pharmaceuticals, Kobe 651-2241, JapanResearch Division, JCR Pharmaceuticals, Kobe 651-2241, JapanResearch Division, JCR Pharmaceuticals, Kobe 651-2241, JapanResearch Division, JCR Pharmaceuticals, Kobe 651-2241, JapanResearch Division, JCR Pharmaceuticals, Kobe 651-2241, JapanResearch Division, JCR Pharmaceuticals, Kobe 651-2241, JapanResearch Division, JCR Pharmaceuticals, Kobe 651-2241, JapanResearch Division, JCR Pharmaceuticals, Kobe 651-2241, JapanHeparan sulfate (HS) is an essential glycosaminoglycan (GAG) as a component of proteoglycans, which are present on the cell surface and in the extracellular matrix. HS-containing proteoglycans not only function as structural constituents of the basal lamina but also play versatile roles in various physiological processes, including cell signaling and organ development. Thus, inherited mutations of genes associated with the biosynthesis or degradation of HS can cause various diseases, particularly those involving the bones and central nervous system (CNS). Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders involving GAG accumulation throughout the body caused by a deficiency of GAG-degrading enzymes. GAGs are stored differently in different types of MPSs. Particularly, HS deposition is observed in patients with MPS types I, II, III, and VII, all which involve progressive neuropathy with multiple CNS system symptoms. While therapies are available for certain symptoms in some types of MPSs, significant unmet medical needs remain, such as neurocognitive impairment. This review presents recent knowledge on the pathophysiological roles of HS focusing on the pathogenesis of MPSs. We also discuss the possible use and significance of HS as a biomarker for disease severity and therapeutic response in MPSs.https://www.mdpi.com/1422-0067/23/19/11724heparan sulfatemucopolysaccharidoseslysosomal storage disorderscerebrospinal fluidbiomarkerblood-brain barrier |
| spellingShingle | Kohtaro Minami Hideto Morimoto Hiroki Morioka Atsushi Imakiire Masafumi Kinoshita Ryuji Yamamoto Tohru Hirato Hiroyuki Sonoda Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses International Journal of Molecular Sciences heparan sulfate mucopolysaccharidoses lysosomal storage disorders cerebrospinal fluid biomarker blood-brain barrier |
| title | Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses |
| title_full | Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses |
| title_fullStr | Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses |
| title_full_unstemmed | Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses |
| title_short | Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses |
| title_sort | pathogenic roles of heparan sulfate and its use as a biomarker in mucopolysaccharidoses |
| topic | heparan sulfate mucopolysaccharidoses lysosomal storage disorders cerebrospinal fluid biomarker blood-brain barrier |
| url | https://www.mdpi.com/1422-0067/23/19/11724 |
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