Neuroprotective role of Noggin in spinal cord injury

Neural Regeneration Research, 2023 · DOI: https://doi.org/10.4103/1673-5374.350190 · Published: March 1, 2023

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injury (SCI) often leads to permanent paralysis due to the difficulty in neuron regeneration. Preventing secondary damage to neurons and glial cells can slow SCI progression by reactivating regenerative proteins like Noggin. Noggin, a natural inhibitor of bone morphogenetic proteins, shows high expression during spinal cord development and after SCI. However, its therapeutic efficacy is debatable as its neuroprotective effects are mainly observed in the early phases of SCI. Clinical information about Noggin's role in alleviating SCI progression, its therapeutic efficacy, bioavailability, and safety in humans is lacking. Further investigation is needed to determine if Noggin can be a potential therapy to improve patient outcomes following SCI.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Noggin shows neuroprotective effects in the early phase of SCI in both in vitro and in vivo models following exogenous Noggin treatment, as well as in SCI in vivo models following therapy with engineered Noggin-expressing cells or implants.
2
The molecular mechanisms for the neuroprotective effect of Noggin in the early phase of SCI occur mostly via the p-Smad1/5/8 pathway and/or the p-signal transducer and activator of transcription 3 (p-STAT3) pathway.
3
Long-term Noggin treatment may increase myelin-producing oligodendroglia cells, promoting remyelination of axons after injury; however, in some studies, Noggin treatment had no significant effect on axonal density and thickness of myelin sheet.

Research Summary

This review discusses the changes in Noggin expression during spinal cord injury (SCI), its neuroprotective role in preclinical models, and the knowledge gap for its use in SCI treatment. The neuroprotective effects of Noggin are mainly observed in the early phases of SCI, with little effect on altering pathogenesis and functional recovery in the chronic phase. Clinical information regarding Noggin's therapeutic efficacy and safety in human SCI is lacking. Noggin treatment has neuroprotective effects in vitro and in vivo during the early stages of SCI, and combining it with other treatments may provide long-term effects, warranting further preclinical investigations to make it translational to the clinics.

Practical Implications

Therapeutic Potential

Noggin shows promise as a therapeutic agent for spinal cord injury, particularly in the early phases, by enhancing oligodendrocyte differentiation and reducing glial scar formation.

Combination Therapies

Combining Noggin treatment with other therapies could potentially augment its neuroprotective effects and provide long-term benefits for SCI patients.

Clinical Trials

Further preclinical and clinical studies are needed to assess the safety, efficacy, and optimal dosage of Noggin for SCI treatment, as well as to understand its long-term effects.

Study Limitations

1
Limited understanding of the cause-effect link and molecular regulation of Noggin in SCI.
2
Lack of data about the effect of high doses of Noggin on other organs and the lowest effective versus toxic dose.
3
Neuroprotective effects of Noggin are demonstrated during the early phases of SCI, and little is known about the long-term effects of Noggin treatment.

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