The MicroRNA Centrism in the Orchestration of Neuroinflammation in Neurodegenerative Diseases.

MicroRNAs (miRNAs) are small non-coding RNAs with a unique ability to regulate the transcriptomic profile by binding to complementary regulatory RNA sequences. The ability of miRNAs to enhance (proinflammatory miRNAs) or restrict (anti-inflammatory miRNAs) inflammatory signalling within the central nervous system is an area of ongoing research, particularly in the context of disorders that feature neuroinflammation, including neurodegenerative diseases (NDDs). Furthermore, the discovery of competing endogenous RNAs (ceRNAs) has led to an increase in the complexity of miRNA-mediated gene regulation, with a paradigm shift from a unidirectional to a bidirectional regulation, where miRNA acts as both a regulator and is regulated by ceRNAs. Increasing evidence has revealed that ceRNAs, including long non-coding RNAs, circular RNAs, and pseudogenes, can act as miRNA sponges to regulate neuroinflammation in NDDs within complex cross-talk regulatory machinery, which is referred to as ceRNA network (ceRNET). In this review, we discuss the role of miRNAs in neuroinflammatory regulation and the manner in which cellular and vesicular ceRNETs could influence neuroinflammatory dynamics in complex multifactorial diseases, such as NDDs.