MicroRNAs: Roles in Regulating Neuroinflammation

• Published in: The Neuroscientist 2018-06, Vol.24 (3), p.221-245
• Main Authors: Gaudet, Andrew D., Fonken, Laura K., Watkins, Linda R., Nelson, Randy J., Popovich, Phillip G.
• Format: Article
• Language: English
• ISSN: 1073-8584; 1089-4098
• DOI: 10.1177/1073858417721150

MicroRNAs (miRNAs) are small noncoding RNAs that broadly affect cellular and physiological function in all multicellular organisms. Here, the role of miRNAs in neuroinflammation is considered. miRNAs are 21- to 23-oligonucleotide RNAs that regulate translation of specific RNAs by binding to complementary regulatory RNA sequences, thereby causing mRNA degradation or sequestration. More than 5000 miRNAs likely exist in humans, and each miRNA binds an average of 200 RNAs. Specific immunomodulatory miRNAs can regulate a set of RNAs in a coordinated manner, suggesting that effective miRNA-based therapeutic manipulations for neuroinflammatory conditions may be revealed. For instance, miRNAs that preferentially inhibit translation of many cellular anti-inflammatory proteins could drive a pro-inflammatory response. Key pro-inflammatory (miR-155, miR-27b, miR-326), anti-inflammatory (miR-124, miR-146a, miR-21, miR-223), and mixed immunomodulatory (let-7 family) miRNAs regulate neuroinflammation in various pathologies, including spinal cord injury, multiple sclerosis, ischemic stroke, and Alzheimer’s disease. miRNAs represent a newly revealed layer of physiological complexity, the therapeutic benefits of which remain to be fully explored and exploited. In this review, we discuss the role of miRNAs in neuroinflammatory regulation and discuss how controlling miRNAs could alter cellular machinery to improve neuroinflammatory dynamics.