title: Inhibitors of myelination: ECM changes, CSPGs and PTPs.
abstract: After inflammation-induced demyelination, such as in the disease multiple sclerosis, endogenous remyelination often fails. However, in animal models of demyelination induced with toxins, remyelination can be quite robust. A significant difference between inflammation-induced and toxin-induced demyelination is the response of local cells within the lesion, including astrocytes, oligodendrocytes, microglia/macrophages, and NG2+ cells, which respond to inflammatory stimuli with increased extracellular matrix (ECM) protein and chondroitin sulfate proteoglycan (CSPG) production and deposition. Here, we summarize current knowledge of ECM changes in demyelinating lesions, as well as oligodendrocyte responses to aberrant ECM proteins and CSPGs after various types of demyelinating insults. The discovery that CSPGs act through the receptor protein tyrosine phosphatase sigma (PTPσ) and the Rho-ROCK pathway to inhibit oligodendrocyte process extension and myelination, but not oligodendrocyte differentiation (Pendleton et al., Experimental Neurology (2013) vol. 247, pp. 113-121), highlights the need to better understand the ECM changes that accompany demyelination and their influence on oligodendrocytes and effective remyelination.
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, 12801 East 17th Avenue, Research Complex 1 South, Mail Stop 8108, Aurora, CO 80045, USA; Center for NeuroScience, University of Colorado School of Medicine, 12801 East 17th Avenue, Research Complex 1 South, Mail Stop 8108, Aurora, CO 80045, USA. Electronic address: Danielle.Harlow@ucdenver.edu.
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Harlow
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, 12801 East 17th Avenue, Research Complex 1 South, Mail Stop 8108, Aurora, CO 80045, USA; Center for NeuroScience, University of Colorado School of Medicine, 12801 East 17th Avenue, Research Complex 1 South, Mail Stop 8108, Aurora, CO 80045, USA. Electronic address: wendy.macklin@ucdenver.edu.
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Macklin
mesh_terms: D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D009186:Myelin Sheath / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000378:metabolism*
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2