Chondroprotectors as modulators of neuroinflammation

Abstract

Modern fundamental and clinical studies show that chondroprotector molecules (chondroitin sulfate – CS; glucosamine sulfate – GS) can be useful in the treatment of neuroinflammation and so-called "inflammageing" – chronic, low-grade systemic inflammation that stimulates the development of neurodegeneration, atherosclerosis, ischemia, osteoarthritis and other pathologies. The role of CS and GS in the central nervous system are evident in the context of the concepts of the tetrapartite synapse and perineuronal nets (PNNs). Molecular mechanisms of action of CS and GS on neuroinflammation include: 1) interaction with the CD44 receptor, leading to inhibition of the pro-inflammatory factor NFκB, antiatherosclerotic and anticoagulant effects; 2) direct contribution to the formation of the PNNs, which support the division and differentiation of neurons; 3) inhibition of Toll-like receptors; 4) antioxidant and neuroprotective properties through activation of the PKC/PI3K/Akt signaling pathway; 5) inhibition of matrix metalloproteinases. These molecular effects determine the neuroprotective properties of CS/GS in ischemia, neurodegeneration, and pain syndromes associated with neuroinflammation.