Insights into the physiological role of CNS regeneration inhibitors

Frontiers in Molecular Neuroscience, 2015 · DOI: 10.3389/fnmol.2015.00023 · Published: June 11, 2015

Simple Explanation

The adult mammalian central nervous system (CNS) contains growth inhibitory factors that hinder axonal regeneration after injury. These inhibitors, like MAG, NogoA, OMgp, and CSPGs, are present in both healthy and injured CNS tissue. These inhibitors regulate myelin development, stabilize neuronal structure, and limit synaptic strength modification. Altered function of these inhibitors is linked to neuropsychiatric disorders. Understanding the function of these molecules in the uninjured CNS is important for developing therapies to promote neural plasticity and nervous system repair.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
MAG plays a crucial role in the maintenance and long-term stability of the axon-glial unit, preventing axonal atrophy with age.
2
NogoA regulates myelin development, with NogoA knockout mice showing reduced OPC differentiation and hypomyelination during development.
3
CSPGs play important roles in visual system development and plasticity, synaptic structure modification, and the protection of memories from erasure.

Research Summary

CNS regeneration inhibitors play important physiological roles in the uninjured brain and spinal cord, regulating myelin formation, axon-myelin interactions, synapse formation, and activity-dependent synaptic strength. These inhibitors participate in cross-talk with growth promoting molecules, influencing key signaling molecules and maintaining a balance of excitation and inhibition in the CNS. Understanding the physiological roles of these molecules is important for developing therapeutic strategies to promote neural regeneration following injury.

Practical Implications

Therapeutic Strategies

Consider the physiological roles of CNS regeneration inhibitors when designing therapies to promote neural regeneration after injury.

Evolutionary Perspective

The acquisition of ligand-receptor systems that restrict neural network plasticity may have been a prerequisite for the evolution of larger, more complex brains.

Clinical Relevance

A deeper understanding of the physiological roles played by CNS regeneration inhibitors is of great interest both clinically and biologically.

Study Limitations

1
The molecular mechanisms employed by MAG to exert its different functions is still incomplete.
2
Compared to MAG and NogoA, significantly less is known about the physiological role of OMgp.
3
Challenges for future studies will be to dissect which CSPGs exert their functions through which receptor complexes and to define their functional relationship to different classes of ligands already known to operate in a LAR family or Nogo receptor family dependent manner.

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