Chondroitin sulfate glycosaminoglycans for CNS homeostasis-implications for material design.
Chondroitin sulfate proteoglycans (CSPGs) are complex biomolecules that are known to facilitate patterning of axonal direction and cell migration during the early growth and development phase of the mammalian central nervous system (CNS). In adults, they continue to control neuronal plasticity as major constituents of the "peri-neuronal nets" (PNNs) that surround adult CNS neurons. CSPGs are also barrier-forming molecules that are selectively upregulated by invading reactive astroglia after injury to the CNS, and are responsible for the active repulsion of regenerating neurons post-injury. Recent evidence however suggests that the diverse sulfated glycosaminoglycan (GAG) side chains attached to CSPGs are key components that play paradoxical roles in influencing nerve regeneration post-injury to the CNS. Sulfated GAG repeats attached to the CSPG core protein help mediate cell migration, neuritogenesis, axonal pathfinding, and axonal repulsion by directly trapping and presenting a whole host of growth factors to cells locally, or by binding to specific membrane bound proteins on the cell surface to influence cellular function. In this review, we will present the current gamut of interventional strategies used to bridge CNS deficits, and discuss the potential advantages of using sulfated GAG based biomaterials to facilitate the repair and regeneration of the injured CNS.
Duke Scholars
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Related Subject Headings
- Medicinal & Biomolecular Chemistry
- Humans
- Homeostasis
- Drug Design
- Chondroitin Sulfate Proteoglycans
- Central Nervous System
- 3404 Medicinal and biomolecular chemistry
- 3214 Pharmacology and pharmaceutical sciences
- 1115 Pharmacology and Pharmaceutical Sciences
- 0601 Biochemistry and Cell Biology
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Medicinal & Biomolecular Chemistry
- Humans
- Homeostasis
- Drug Design
- Chondroitin Sulfate Proteoglycans
- Central Nervous System
- 3404 Medicinal and biomolecular chemistry
- 3214 Pharmacology and pharmaceutical sciences
- 1115 Pharmacology and Pharmaceutical Sciences
- 0601 Biochemistry and Cell Biology