RNA regulation of inflammatory responses in glia and its potential as a therapeutic target in central nervous system disorders

A major hallmark of neuroinflammation is the activation of microglia and astrocytes with the induction of inflammatory mediators such as IL-1 beta, TNF-alpha, iNOS, and IL-6. Neuroinflammation contributes to disease progression in a plethora of neurological disorders ranging from acute CNS trauma to chronic neurodegenerative disease. Posttranscriptional pathways of mRNA stability and translational efficiency are major drivers for the expression of these inflammatory mediators. A common element in this level of regulation centers around the adenine- and uridine-rich element (ARE) which is present in the 3 ' untranslated region (UTR) of the mRNAs encoding these inflammatory mediators. (ARE)-binding proteins (AUBPs) such as Human antigen R (HuR), Tristetraprolin (TTP) and KH- type splicing regulatory protein (KSRP) are key nodes for directing these posttranscriptional pathways and either promote (HuR) or suppress (TTP and KSRP) glial production of inflammatory mediators. This review will discuss basic concepts of ARE-mediated RNA regulation and its impact on glial-driven neuroinflammatory diseases. We will discuss strategies to target this novel level of gene regulation for therapeutic effect and review exciting preliminary studies that underscore its potential for treating neurological disorders.

Automated summary

Neuroinflammation is characterized by the activation of microglia and astrocytes, leading to the production of inflammatory mediators. The regulation of mRNA stability and translational efficiency plays a crucial role in the expression of these mediators. The adenine- and uridine-rich element (ARE) present in the mRNA's untranslated region (UTR) is a key factor in this regulation. This review discusses the impact of ARE-mediated RNA regulation on glial-driven neuroinflammatory diseases.