Journal
FEBS LETTERS
Volume 592, Issue 23, Pages 3791-3805Publisher
WILEY
DOI: 10.1002/1873-3468.13026
Keywords
central nervous system; chondroitin sulfate; extracellular matrix; glycosaminoglycans; heparan sulfate; Proteoglycans; proteoglycan-interacting molecules
Funding
- National Institute of Child Health and Human Development [NICHD: PO1 HD 09402, R01 HD 017332]
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Proteoglycans are diverse, complex extracellular/cell surface macromolecules composed of a central core protein with covalently linked glycosaminoglycan (GAG) chains; both of these components contribute to the growing list of important bio-active functions attributed to proteoglycans. Increasingly, attention has been paid to the roles of proteoglycans in nervous tissue development due to their highly regulated spatio/temporal expression patterns, whereby they promote/inhibit neurite outgrowth, participate in specification and maturation of various precursor cell types, and regulate cell behaviors like migration, axonal pathfinding, synaptogenesis and plasticity. These functions emanate from both the environments proteoglycans create around cells by retaining ions and water or serving as scaffolds for cell shaping or motility, and from dynamic interactions that modulate signaling fields for cytokines, growth factors and morphogens, which may bind to either the protein or GAG portions. Also, genetic abnormalities impacting proteoglycan synthesis during critical steps of brain development and response to environmental insults and injuries, as well as changes in microenvironment interactions leading to tumors in the central nervous system, all suggest roles for proteoglycans in behavioral and intellectual disorders and malignancies.
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