Low-Molecular Weight Protamine Overcomes Chondroitin Sulfate Inhibition of Neural Regeneration

Front. Cell Dev. Biol., 2022 · DOI: 10.3389/fcell.2022.865275 · Published: April 25, 2022

Simple Explanation

Following a spinal cord injury, the body produces molecules that inhibit the regeneration of nerve fibers. This study investigates a peptide called protamine and a smaller fragment, low-molecular weight protamine (LMWP), to counteract these inhibitory molecules. The researchers found that protamine fragments, particularly LMWP, can overcome the inhibition of nerve fiber growth caused by chondroitin sulfate proteoglycans (CSPGs). Animal studies showed that LMWP enhances recovery from spinal cord injuries, suggesting it could be a potential drug lead for treating CNS injuries.

Study Duration

Not specified

Participants

Mice, rat embryos (E17 Wistar rats), primary CNS neurons

Evidence Level

In vitro and in vivo study

Key Findings

1
LMWP overcomes the neurite outgrowth inhibition by CSPGs in vitro, mimicking the effects of HB-GAM.
2
LMWP exhibits very low or no toxicity in vitro and in vivo, unlike the full-length protamine which shows toxicity.
3
In vivo studies using SCI models in mice revealed that LMWP enhances recovery when administered through intracerebroventricular or systemic routes.

Research Summary

This study demonstrates that protamine and its fragments, specifically LMWP, can block the inhibitory effect of CSPGs on neurite growth. LMWP enhances recovery in spinal cord hemisection and hemicontusion models in mice, suggesting its potential as a drug lead for CNS injuries. Systemic administration of LMWP enhances axonal regeneration in spinal cord hemicontusion.

Practical Implications

Drug Development

LMWP is a promising drug lead for developing therapies for CNS injuries, particularly spinal cord injuries.

Overcoming Glial Scar Inhibition

LMWP can overcome the inhibition of neural regeneration caused by the glial scar, a major obstacle in CNS injury recovery.

Systemic Administration Potential

LMWP can be administered systemically, offering a convenient route for potential human therapies.

Study Limitations

1
Further studies are required to define the optimal dose and pharmacokinetics of LMWP when administered through the systemic route.
2
Further studies are required to define whether regeneration of descending axonal tracts or local sprouting of interneurons is affected.
3
The study is limited by the use of animal models, and the results may not directly translate to human patients.

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