Chondroitin Sulfate Proteoglycans Revisited: Its Mechanism of Generation and Action for Spinal Cord Injury

Aging Dis. 2024 Feb 1;15(1):153-168. doi: 10.14336/AD.2023.0512.

Abstract

Reactive astrocytes (RAs) produce chondroitin sulfate proteoglycans (CSPGs) in large quantities after spinal cord injury (SCI) and inhibit axon regeneration through the Rho-associated protein kinase (ROCK) pathway. However, the mechanism of producing CSPGs by RAs and their roles in other aspects are often overlooked. In recent years, novel generation mechanisms and functions of CSPGs have gradually emerged. Extracellular traps (ETs), a new recently discovered phenomenon in SCI, can promote secondary injury. ETs are released by neutrophils and microglia, which activate astrocytes to produce CSPGs after SCI. CSPGs inhibit axon regeneration and play an important role in regulating inflammation as well as cell migration and differentiation; some of these regulations are beneficial. The current review summarized the process of ET-activated RAs to generate CSPGs at the cellular signaling pathway level. Moreover, the roles of CSPGs in inhibiting axon regeneration, regulating inflammation, and regulating cell migration and differentiation were discussed. Finally, based on the above process, novel potential therapeutic targets were proposed to eliminate the adverse effects of CSPGs.

Publication types

  • Review

MeSH terms

  • Axons / metabolism
  • Chondroitin Sulfate Proteoglycans* / metabolism
  • Humans
  • Inflammation
  • Nerve Regeneration
  • Spinal Cord Injuries* / drug therapy

Substances

  • Chondroitin Sulfate Proteoglycans

Grants and funding

This work is supported by the following funding sources. Grant support was provided by the National Natural Science Fund of China [grant numbers 81771346, 82071383], Natural Science Foundation of Shandong Province (Key Project) [grant numbers ZR2020KH007], the Taishan Scholar Youth Program of Shandong Province [grant numbers tsqn201812156], Academic Promotion Program of Shandong First Medical University [grant numbers 2019QL025, 2019RC021], Spring Industry Leader Talent Support Plan [grant numbers 201984], and Rongxiang Regenerative Medicine Fund [grant numbers 2019SDRX-23] (all to BN).