| OCR Text |
Show 180 significantly at body temperature (8). Therefore, Lee et al. have reported the use of trehalose to thermostablize ChABC and prolonging its activity. The stabilized enzyme could digest CS chains in vivo up to two weeks postinjury (9). Another concern with the use of ChABC is complete degradation of CS chains that may lead to loss of growth promoting or guiding motifs. Therefore, as demonstrated in Chapter 4, click-xylosides can be used for partially underglycosylating CSPGs and lead to better therapeutic outcomes than ChABC. Takeuchi et al. have recently shown that by knocking out CS N-acetylgalactosaminyltransferase-(T1), the enzyme responsible for CS synthesis, mice recover more completely from spinal cord injuries than the ChABC-treated mice (10). This implies that the inhibition of glycosylation of PGs holds tremendous potential for CNS therapy. Such an approach may also be beneficial in Alzheimer's disease and schizophrenia, where upregulation of HS or CS leads to disease progression. Partial or complete digestion of such GAG structures with combinations of various xyloside structures could be explored for functional effective restorations recovery in such disorders. Enzymes such as Chondroitinase AC or Chondroitinase B should also be explored to selectively remove inhibitory motifs and lead to better therapeutic outcomes than ChABC. Previously, our lab has shown that click-xylosides containing various aglycone residues can prime a variety of different GAGs in Chinese hamster ovary (CHO) cells (11). Additionally, β-D-xylosides have been used on astrocytes to enhance neuronal growth (12). Moreover, 4-deoxy-4-fluoro xylosides (fluoro-xylosides) could be exploited to inhibit GAG production at the |
