miR-142-3p is a Potential Therapeutic Target for Sensory Function Recovery of Spinal Cord Injury

Medical Science Monitor, 2015 · DOI: 10.12659/MSM.894098 · Published: August 28, 2015

Simple Explanation

Spinal cord injury (SCI) is a leading cause of disability, often resulting from trauma. Sciatic nerve conditioning injury has shown promise in repairing the ascending spinal sensory pathway in animals, but it's ethically challenging to apply in clinical settings. The article proposes miR-142-3p as a key therapeutic target for restoring sensory function after SCI. Studies suggest endogenous cAMP, regulated by miR-142-3p, elevates cAMP via adenylyl cyclase 9 (AC9) in dorsal root ganglia (DRG), promoting neurite growth. Inhibiting microRNA in DRG is less invasive than gene regulation in the injured spinal cord. This suggests a novel approach to enhance central regeneration of primary sensory neurons. The proposed mechanism involves imitating sciatic nerve conditioning injury by interfering with the congenerous upstream regulator AC9 of three signal pathways. This approach aims to provide a new clinical treatment strategy for the recovery of sensory function in SCI patients.

Study Duration

Not specified

Participants

Laboratory animals

Evidence Level

Hypothesis

Key Findings

1
miR-142-3p can induce cAMP elevation via adenylyl cyclase 9 (AC9), which is abundant in dorsal root ganglia (DRG).
2
Inhibition of microRNA (miRNA) in DRG is less likely to cause trauma and infection compared with gene expression regulation in the injured spinal cord.
3
Downregulation of miR-142-3p can effectually upregulate the final level of cAMP via upregulating the expression of AC9 in injured neurons of DRG.

Research Summary

The article hypothesizes that miR-142-3p is the upstream molecular basis for sciatic nerve transection enhancing central regeneration of primary sensory neurons, and that it is a potential therapeutic target for sensory function recovery of spinal cord injury. The suggested mechanism involves the downregulation of miR-142-3p, which upregulates AC9 expression, leading to increased cAMP levels and subsequent activation of three signal pathways promoting neuronal regeneration. The authors conclude that miR-142-3p is a novel regulatory gene of the upstream molecular mechanism for sciatic nerve conditioning injury and suggest further study is needed to test this hypothesis.

Practical Implications

Therapeutic Target

miR-142-3p presents a potential therapeutic target for gene therapy aimed at sensory function recovery in SCI patients.

Mimicking Sciatic Nerve Conditioning

Interfering with AC9, the congenerous upstream regulator, can imitate the beneficial effects of sciatic nerve conditioning injury without the associated ethical concerns.

Less Invasive Intervention

Intervention in DRG, compared to gene expression regulation in the injured spinal cord, reduces trauma and infection risks.

Study Limitations

1
Further study is needed to test this hypothesis
2
Influence of miR-142-3p on other genes needs examination using mRNA microarray.
3
Need to avoid injury to the DRG neurons during administration of miR-142-3p in DRG.

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