MicroRNAs in Neurodevelopment and Their Relationship with Neurological, Neuropsychiatric and Neurodegenerative Diseases

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level and play important roles in the development and function of the nervous system. Through the coordinated regulation of multiple target genes and signalling pathways, miRNAs participate in key neurodevelopmental processes, including neural progenitor proliferation and differentiation, neuronal specification and migration, morphological maturation, synaptic development, and circuit formation. Their functions are strongly dependent on developmental stage, cell type, brain region, and expression level, and the extent of mechanistic characterization varies considerably among individual miRNAs. This review examines well-characterized and emerging neurodevelopment-related miRNAs, including members of the miR-9, miR-34, miR-107, miR-124, miR-132, miR-134, miR-137, miR-181, miR-185, miR-191, miR-200, miR-218, and miR-344 families, integrating evidence on their molecular mechanisms and functions during nervous system development. Their dysregulation is further considered in neurodevelopmental, neuropsychiatric, neurological, and neurodegenerative disorders, as well as in selected rare and metabolic or endocrine disorders with neurological involvement. We also examine the potential of circulating and tissue-associated miRNAs as diagnostic and prognostic biomarkers and the emerging therapeutic possibilities of miRNA modulation. Current evidence supports important roles for miRNAs in neurodevelopment and neurological disease but also highlights substantial differences between mechanistic and associative evidence. Methodological heterogeneity, differences between central and peripheral miRNA profiles, limited independent validation, and challenges associated with targeted delivery and off-target effects remain major barriers to their clinical translation.