Exploring Non-Coding RNA Regulation of the Blood–Brain Barrier in Neurodegenerative Diseases: A Systematic Review

Neurodegenerative diseases (NDs) are characterized by progressive neuronal loss and dysfunction, leading to significant cognitive and motor impairments. The disruption of the blood–brain barrier (BBB) integrity, a key regulator of central nervous system homeostasis, emerges as a critical factor in the pathogenesis of these disorders. Accumulating evidence implicates non-coding RNAs, particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in BBB regulation. However, the intricate network governing BBB dysfunction and consequent neurodegeneration remains obscure. This systematic review maps the convergent microRNA networks in Alzheimer's, Parkinson's, and multiple sclerosis, unveiling their putative roles in BBB modulation. We analyzed data from 11 peer-reviewed clinical studies, identifying key miRNAs such as hsa-miR-155, hsa-miR-22, hsa-miR-146a, hsa-miR-100-3p, and hsa-miR-182-5p as critical regulators of BBB permeability and inflammatory responses. Enrichment analysis revealed that these miRNAs modulate pathways related to inflammation, oxidative stress, and neuronal survival. Our review also uncovered extensive interactions between these miRNAs and transcription factors like JUN, RELA, STAT3, and TP53, as well as lncRNAs such as MALAT1, NEAT1, NORAD, and SNHG16. These interactions highlight complex regulatory networks involving miRNA sponging and chromatin remodeling, which may play crucial roles in maintaining BBB integrity. These analyses underscore the importance of miRNA-mediated regulatory networks in BBB function and offer insights into potential therapeutic targets for NDs. (Figure presented.)