Chondroitin Sulfate Proteoglycans in the Nervous System: Inhibitors to Repair

BioMed Research International, 2014 · DOI: 10.1155/2014/845323 · Published: September 18, 2014

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Chondroitin sulfate proteoglycans (CSPGs) are molecules present in the central nervous system that guide development and adjust synaptic connections. After injury or disease, CSPG expression increases near the damaged areas. However, CSPG deposits hinder regeneration, preventing repair in the brain and spinal cord. This review discusses CSPGs as inhibitors, the role of inflammation in increasing CSPG expression, and therapeutic strategies to overcome CSPG's inhibitory effects and promote nerve regeneration. Injuries to the CNS can generally be classified into two overarching categories: traumatic and neurodegenerative.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
CSPGs are upregulated rapidly in the tissue surrounding a lesion site, due to the induction of reactive gliosis.
2
The bacterial enzyme chondroitinase ABC (cABC) can neutralize the inhibitory nature of the CSPG molecules and thus was tested in many injury models, resulting in increased axonal sprouting, growth, and plasticity.
3
Xyloside blocks the attachment of the GAGs to the CSPG’s central core protein, which is the primary inhibitory element of CSPGs, promoting tissue repair.

Research Summary

Following any insult to the CNS, traumatic or degenerative, an inflammatory reaction occurs, and the activation of microglia, astrocytes, and invasion of vascular macrophages result in an upregulation and synthesis of CSPGs. CSPGs form an important protective barrier, preventing further secondary tissue damage, but is also a primary reason axonal regeneration and remyelination fails following any type of injury to the CNS. Modification of CS-GAG expression on CSPGs, while not completely ablating the CSPG molecule, is a reasonable approach to facilitating repair.

Practical Implications

Therapeutic target

Modifying CS-GAG expression on CSPGs is a reasonable therapeutic approach to facilitating repair in the damaged CNS.

Chondroitinase ABC Use

Administration of cABC at the site of a CNS lesion to remove the inhibitory GAG chains and neutralize the inhibitory nature of CSPGs can improve motor function.

Combination Therapies

cABC will need to be used in conjunction with agents such as neurotrophins that can directly promote neuronal survival and stimulate axonal growth.

Study Limitations

1
Long distance axonal regeneration is rarely observed with cABC treatment alone.
2
cABC is a labile enzyme, losing activity quickly in solution.
3
Excess cABC would destabilize perineuronal nets in uninjured tissue, which could potentially result in aberrant axonal sprouting and circuit formation as well as synaptic instability.

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