Multifunctions of Sustainable Chondroitin Sulfates with Predominant Subtypes and Low Molecular Weights on Neurite Outgrowth

Three chondroitin sulfate (CS) analogues with predominant subtypes (A, C, and E) were prepared from engineered Escherichia coli K4 combined with regioselective sulfation. CS with the designed sulfates as the main components was characterized by nuclear magnetic resonance spectroscopy, elementary analysis, and disaccharide analysis. CS prepared from the native or degraded capsular polysaccharide had molecular weights of 1.55 × 104–1.90 × 104 and 5.6 × 103–7.4 × 103, respectively. We found that CS with dual sulfates promoted the outgrowth and survival of hippocampal neurons, whereas CS with monosulfate had an inhibitory effect. CS interacted with the nerve growth factor (NGF) and tyrosine kinase (TrkA), which activated the extracellular signal-regulated kinase (ERK) signaling pathway to modulate the outgrowth of hippocampal neurons. This work clarified the multiple effects of CS on neurite outgrowth based on nonanimal-sourced glycosaminoglycans, which would benefit efforts in discovering their novel functions and therapeutic applications.