MicroRNAs: Roles in Regulating Neuroinflammation

Abstract

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.

Targeting vascular inflammation in ischemic stroke: Recent developments on novel immunomodulatory approaches

“…A full accounting of the potential role of miRNAs as therapeutic targets or agents for ischemic stroke is beyond the scope of our review and the reader is referred to some recent articles on the topic (Chandran et al, 2017; Gaudet et al, 2017; Kaur et al, 2018; Khoshnam et al, 2017). Rather, we focus on several miRNAs that have garnered considerable interest and are illustrative of the potential benefits and challenges of this approach.…”

“…miR-124 is highly expressed in the nervous system and is considered anti-inflammatory (Gaudet et al, 2017). Early in ischemic stroke it is released by damaged neurons and is upregulated by the anti-inflammatory Th2 cytokines Il-4 and IL-13 (Rayasam et al, 2017).…”

“…Early in ischemic stroke it is released by damaged neurons and is upregulated by the anti-inflammatory Th2 cytokines Il-4 and IL-13 (Rayasam et al, 2017). miR-124 plays a critical role in polarizing myeloid cells towards the M2 anti-inflammatory phenotype in part by targeting components of IL-6 and TNF-α signaling (Gaudet et al, 2017; Rayasam et al, 2017). But miR-124 also attenuates toll-like receptor signaling that likely is important for tissue repair (Gaudet et al, 2017).…”

“…miR-124 plays a critical role in polarizing myeloid cells towards the M2 anti-inflammatory phenotype in part by targeting components of IL-6 and TNF-α signaling (Gaudet et al, 2017; Rayasam et al, 2017). But miR-124 also attenuates toll-like receptor signaling that likely is important for tissue repair (Gaudet et al, 2017). Evidence from several rodent studies have provided support for the idea that miR-124 is neuroprotective when delivered acutely by polarizing brain microglia/macrophages towards an anti-inflammatory M2 phenotype (Doeppner et al, 2013; Hamzei Taj et al, 2016; Sun et al, 2013).…”

MiR‐409‐3p and MiR‐1896 co‐operatively participate in IL‐17‐induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling

“…MiRNAs are implicated in regulating CNS diseases and the development of autoimmune diseases, including MS. Some miRNAs are proposed as potential biomarkers for the diagnosis and prognosis of neurological diseases (Chen, Papp, Szodoray, & Zeher, 2016;Gaudet, Fonken, Watkins, Nelson, & Popovich, 2017;Sheinerman & Umansky, 2013). MiR-326 was shown to promote Th-17 differentiation and to be positively correlated with IL-17 production in MS patients (Du et al, 2009).…”