Neuronal growth cones and regeneration: gridlock within the extracellular matrix

Neural Regen Res, 2014 · DOI: 10.4103/1673-5374.128234 · Published: February 1, 2014

Regenerative Medicine Neurology Genetics

Simple Explanation

The extracellular matrix (ECM) in the central nervous system is a dynamic structure that is constantly being reshaped. Maladaptive responses of the ECM can hinder axonal regeneration after injuries. Chondroitin sulfate proteoglycans (CSPGs) are a major focus of research due to their role in axonal injury and regeneration. Researchers are exploring how to modify the inhibitory aspects of CSPGs while preserving their beneficial components. Matrix metalloproteinases (MMPs) are natural degradation enzymes that reorganize CSPGs, playing a role in neuroplasticity and synapse formation after CNS injury.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Not specified

Key Findings

1
Specific receptors for CSPGs have been identified, suggesting that CSPGs inhibit axon growth through multiple mechanisms, opening new avenues for therapeutic development.
2
MMPs interact with immune molecules to mediate cellular responses in the regenerative environment and are regulated by binding partners in the brain ECM.
3
Glial cells react to CNS injury by changing ECM components, attempting to cordon off the insult for repair and minimize damage, but these changes can become chronic.

Research Summary

This review discusses the extracellular matrix (ECM) and its role in axonal outgrowth regulation following central nervous system (CNS) injury, focusing on proteoglycan structure and function. It highlights the importance of understanding proteoglycan receptors and degradation mechanisms, as well as related immune responses, in the context of neural regeneration. The review also celebrates contributions from young researchers who are driving advancements in the field of ECM research related to spinal cord and brain injuries.

Practical Implications

Therapeutic Targets

Identifying specific CSPG receptors opens avenues for developing targeted therapies to promote axonal regeneration.

Modulating Immune Response

Understanding the interaction between MMPs and immune molecules can lead to strategies for modulating the immune response to promote repair after CNS injury.

Minimizing Chronic Injury

Modifying the inhibitory perilesion microenvironment, while preserving protective glial cell functions, could help to reduce chronic injury after CNS damage.

Study Limitations

1
Stability and delivery issues with chondroitinase ABC limit its clinical application.
2
The complexity of CSPG glycosylation challenged receptor identification.
3
Deleterious changes in the ECM do not rapidly resolve as one sees in the periphery

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