Structural Variation of Chondroitin Sulfate and Its Roles in the Central Nervous System
Abstract
Chondroitin sulfate is popular in the field of neuroscience, because the treatment of nervous tissues with chondroitinase ABC, which degrades chondroitin sulfate up to unsaturated disaccharides, causes severe changes in various aspects of neural development and functions. Chondroitinase ABC treatments of developing nervous tissue impair the growth and differentiation of neural progenitor cells, and cause various pathfinding errors of axons. After injury to the adult central nervous system, axon regeneration fails at scar regions expressing large amounts of chondroitin sulfate proteoglycans. However, after chondroitinase ABC treatment, many axons regenerate and traverse the damaged areas. Furthermore, it was revealed that chondroitin sulfate proteoglycans are involved in neural plasticity. These observations indicated that chondroitin sulfate proteoglycans as major components of the extracellular matrix and cell surface play pivotal roles in the development, regeneration, and plasticity of neuronal networks. Chondroitin sulfate shows highly diverse structural variation, and recent studies indicated that this glycosaminoglycan binds with various growth factors, chemokines and axon guidance molecules in a structure-dependent manner and regulates their activities. Notably, oversulfated structures such as D (GlcA(2-O-sulfate)beta 1-3GalNAc(6-O-sulfate)) and E (GlcAbeta1-3GalNAc(4,6-O-disulfate)) units constitute the binding sites for many proteins, and play important roles in regulation of the growth of neural progenitors, neurite extension, and neuronal migration. The synthesis of these structures is strictly regulated by the chondroitin sulfate synthase family and many sulfotransferases, which should be useful therapeutic targets in neurological disorders.
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CSPGs are composed of specific core proteins to which chondroitin sulfate chains are attached.
“CSPGs are composed of specific core proteins to which chondroitin sulfate (CS) chains are attached42”
From Aggrecan and chondroitin-6-sulfate abnormalities in schizophrenia and bipolar disorder: a postmortem study on the amygdala (2015) · cites this paper as [42]
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- Authors
- Maeda, N.
- Corresponding author
- Maeda, Nobuaki
- ORCID
- Maeda, Nobuaki
- Venue
- Central Nervous System Agents in Medicinal Chemistry
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2010-03-01
- Volume
- 10
- Issue
- 1
- Pages
- 22-31
- ISSN
- 1568-0150 (ISSN-L)
- 1871-5249
- OpenAlex
- W1986151194
- Cited by
- 43
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 6 · 2021: 3 · 2020: 7 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 5 · 2014: 5 · 2013: 1 · 2012: 3
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Central Nervous System Agents in Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (22570149)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- chondroitin sulfate, chondroitin sulfate proteoglycans, chondroitinase ABC, glycosaminoglycan structure, sulfated disaccharides, neural progenitor cells, axon regeneration, axon guidance, neuroplasticity, extracellular matrix, sulfotransferase, growth factor binding, chemokines, neuronal migration, neurite outgrowth, central nervous system injury
- MeSH terms
- Animals, Brain, Brain Chemistry, Carbohydrate Conformation, Carbohydrate Sequence, Central Nervous System, Chondroitin Sulfates, Molecular Sequence Data, Chondroitin Sulfate Proteoglycans, Structure-Activity Relationship, Sulfotransferases, Molecular Structure, Chondroitin ABC Lyase
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