Microglia-derived microRNAs: A potential player in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS)

✍️ Author: Dr Eleni Christoforidou

🕒 Approximate reading time: 4 minutes

Microglia, the primary immune cells of the central nervous system, play a critical role in maintaining neuronal health and responding to injury or disease. Emerging evidence suggests that microglia-derived microRNAs (miRNAs) could be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease characterised by the progressive loss of motor neurons in the brain and spinal cord.

MicroRNAs: Small but Powerful Regulators

MicroRNAs are small, non-coding RNA molecules that regulate gene expression post-transcriptionally. By binding to complementary sequences in target messenger RNAs (mRNAs), miRNAs can suppress translation or promote mRNA degradation, ultimately modulating the levels of specific proteins. Given their regulatory roles, dysregulation of miRNA expression or function has been implicated in various diseases, including neurodegenerative disorders like ALS.

Microglia-derived MicroRNAs and ALS

Several lines of evidence suggest that microglia-derived miRNAs could contribute to the pathogenesis of ALS:

1. Altered miRNA expression: Studies have shown that the expression of specific miRNAs is altered in microglia in both ALS patients and animal models of the disease. These changes in miRNA expression can influence the production of various proteins involved in neuroinflammation, motor neuron survival, and other cellular processes relevant to ALS pathology.

2. Neuroinflammation: Microglia-derived miRNAs can modulate the inflammatory response in the central nervous system. In ALS, dysregulated miRNA expression may contribute to a chronic pro-inflammatory state, which can exacerbate motor neuron degeneration.

3. Neuron-microglia communication: miRNAs can be secreted by microglia and taken up by neighboring neurons, influencing their gene expression and function. In the context of ALS, this intercellular communication may contribute to the spread of disease pathology and motor neuron dysfunction.

Therapeutic Implications

The potential involvement of microglia-derived miRNAs in ALS pathogenesis raises the possibility of targeting these molecules or their associated pathways for therapeutic intervention. Some potential strategies include:

1. Modulating miRNA expression or function: Small molecules, antisense oligonucleotides, or other therapeutic agents could be used to modulate the expression or function of specific miRNAs implicated in ALS pathology, potentially ameliorating neuroinflammation and motor neuron degeneration.

2. Enhancing neuron-microglia communication: Promoting beneficial neuron-microglia communication by modulating miRNA secretion or uptake could help counteract the detrimental effects of dysregulated miRNA expression in ALS.

3. Combination therapies: Given the complex nature of ALS, combining miRNA-based therapies with other approaches targeting different aspects of the disease may provide the most effective treatment strategy.

Conclusion

Microglia-derived microRNAs have emerged as potential players in the pathogenesis of amyotrophic lateral sclerosis (ALS), with roles in neuroinflammation, motor neuron survival, and neuron-microglia communication. Targeting these miRNAs or their associated pathways could represent a promising therapeutic strategy for ALS. Continued research on the role of microglia-derived miRNAs in neurodegenerative diseases will be crucial for advancing our understanding of ALS and developing novel treatments to slow or halt the progression of the disease.