MiRNAs as Promising Translational Strategies for Neuronal Repair and Regeneration in Spinal Cord Injury

Cells, 2022 · DOI: 10.3390/cells11142177 · Published: July 12, 2022

Simple Explanation

Spinal cord injury (SCI) is a devastating condition affecting mobility and sensory function. Current treatments are limited, but miRNAs, crucial for neural cell differentiation and pathological processes after SCI, show promise as therapeutic candidates. MiRNA replacement therapy aims to transfer miRNAs to diseased cells, improving targeting efficacy and promoting SCI repair while reducing functional deficits. This review provides an overview of pre-clinical evidence evaluating miRNA therapy in SCI, focusing on miRNAs associated with neuronal and axon regeneration to promote SCI repair and reduce functional deficits.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
MiR-7b-3p, upregulated after SCI, targets Wipf2, protecting cortical neurons from apoptosis and maintaining plasticity.
2
MiRNA-124 improves neuronal loss and reduces astrocyte activation, increasing neurofilament-200 expression. It promotes neural stem cell migration and induces neuron-specific differentiation.
3
Inhibition of miR-448 protects neurons from apoptosis, promotes motor neuron regeneration, and improves motor function by modulating the PI3K/AKT/Bcl-2 pathways.

Research Summary

This review explores the potential of microRNAs (miRNAs) as therapeutic interventions for spinal cord injury (SCI), focusing on their role in neuronal repair and axonal regeneration. It highlights the pathophysiology of SCI, detailing the potential role of miRNAs in the pathological process. The review summarizes preclinical evidence evaluating the use of miRNA therapy in SCI, emphasizing miRNAs widely associated with neuronal and axon regeneration. It discusses the biogenesis, structure, and function of miRNAs, and their expression in SCI. The manipulation of miRNA expression may provide an opportunity to develop improved therapeutic and clinical interventions to address the consequences of SCI since they promote axonal growth, cell regeneration, neuroplasticity, and facilitates functional recovery.

Practical Implications

Therapeutic Target Identification

MiRNAs represent potential therapeutic targets for SCI due to their involvement in neuronal and axonal regeneration.

Biomarker Development

Changes in miRNA expression can be used as biomarkers for detecting and regulating post-traumatic and neurodegenerative processes in SCI.

Clinical Interventions

MiRNA-based therapies, such as miRNA replacement, offer a promising technique to promote SCI repair and reduce functional deficits.

Study Limitations

1
Avoiding degradation by circulating RNAases or in the endocytic compartment of cells is a major challenge in miRNA-based therapies.
2
Potential off-target effects of miRNA imitations can induce unwanted side effects or counteract protective effects.
3
The need to penetrate the blood-brain barrier (BBB) complicates the administration of miRNAs for CNS lesions.

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