CircRNA-Based Therapeutics: a New Frontier in Neuroinflammation Treatment

Neuroinflammation is a complicated and multifactorial reaction in the central nervous system (CNS) that contributes to the pathophysiology of many neurological illnesses, such as neurodegenerative diseases and traumatic brain injury. Circular RNAs (circRNAs) have been identified to play important regulatory roles in neuroinflammatory diseases, making for novel therapeutic concerns. This review provides an overview of recent studies targeting the modulation of circRNA to aid in neuroinflammation, utilizing both silencing and overexpression strategies to facilitate possible neuron protection from neuroinflammatory insults. Studies using silencing approaches, such as siRNA or shRNA, have provided evidence that targeting specific circRNAs, like circHIPK2, circMETTL9, and circCDC14A, can be achieved by regulating various biomolecules, including STAT3, chemokines, and p38 MAPK. In contrast, using plasmid or mimic transfection to overexpress circRNAs, such as circ_DLGAP4, circRNA001372, circDYM, and circDlgap4, demonstrates some potential to also enhance anti-inflammatory effects by targeting NF-κB and HSP90. Studies examining the relationships between circ-Shank3/TLR4, circ-CDR1as/TRAF3, and circ_0008146/Cx3cr1 further demonstrate that these axes influence the modulation of neuroinflammation in response to various activators. The objective of this review is to offer a comprehensive overview of the findings on circRNAs to date while reviewing the various mechanisms by which circRNAs have been described to affect neuroinflammation and also consider the possible future therapeutic applicability for circRNAs in this setting.