Exosomal MiRNA Therapy for Central Nervous System Injury Diseases

Cellular and Molecular Neurobiology, 2025 · DOI: https://doi.org/10.1007/s10571-024-01522-0 · Published: November 25, 2024

Neurology Genetics

Simple Explanation

Central nervous system diseases include injuries, neurodegenerative conditions, and other disorders. MicroRNAs (miRNAs) are key gene expression regulators with therapeutic potential for central nervous system injuries. Exosomal miRNAs show promise in treating traumatic brain injury, stroke, hemorrhage, optic nerve injury, and spinal cord injury. Exosomes, with a lipid bilayer structure like parent cells, effectively penetrate physiological barriers, promoting cell communication. Mesenchymal stem cell-derived exosomes are commonly used for local administration. Viral and non-viral techniques enhance miRNA abundance in exosomes. MiRNA delivery methods include intranasal, intravitreal, nerve injury site, intracerebroventricular, intraspinal, and intravenous injections. The choice depends on treatment needs. This review outlines the latest miRNA-based therapeutic advancements for central nervous system injury diseases.

Study Duration

Not specified

Participants

Animal models (mice/rats)

Evidence Level

Review Paper

Key Findings

1
Exo-miR-124 facilitates M2 polarization of microglia through the inhibition of the TLR4 pathway, thereby affecting hippocampal neurogenesis and the recovery of neurological behavior and cognition after TBI.
2
Exo-miR-17-92 reduces neuroinflammation and neuronal cell loss, increases neurogenesis and angiogenesis, and significantly improves the therapeutic efficacy of functional recovery after TBI.
3
Exo-miR-126 promotes angiogenesis and neurogenesis, inhibits apoptosis, and enhances functional recovery after SCI by suppressing the expression of SPRED1 and PIK3R2.

Research Summary

This review comprehensively examines the therapeutic potential of exosomal miRNAs in treating various central nervous system injury diseases. It covers traumatic brain injury, ischemic stroke, intracerebral hemorrhage, optic nerve injury, and spinal cord injury. The review details the pathophysiology of CNS injuries, animal models used in research, methods of miRNA transfection and administration, and behavioral tests to evaluate treatment effectiveness. It also discusses the mechanisms of action of miRNA-based therapies. The paper also highlights the importance of developing efficient delivery methods for miRNAs that can specifically target the desired location within the CNS and explores the potential for synergistic effects through the simultaneous delivery of multiple miRNAs.

Practical Implications

Therapeutic Target Identification

MiRNAs like miR-124, miR-17-92, and miR-126 show promise as therapeutic targets for CNS injuries due to their roles in modulating neuroinflammation, neurogenesis, and angiogenesis.

Delivery Method Optimization

The development of efficient delivery methods for miRNAs is crucial for targeted treatment within the CNS, with intranasal administration offering unique advantages.

Synergistic Treatment Strategies

Exploring the combined use of multiple miRNAs could enhance treatment safety and efficacy by inducing synergistic effects, reducing drug dosages, and minimizing side effects.

Study Limitations

1
Limited understanding of specific neural targets for miRNA therapy after nerve injury.
2
Potential systemic side effects due to lack of specific markers for miRNA's ability to regulate multiple gene expressions.
3
The challenge of predicting the specific effects of miRNA on the site of nerve injury due to their multifaceted functions and interactions with different cell types.

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