Biological pathways related to mirna-125a-5p in behavioral variant of frontotemporal dementia

Frontotemporal dementia (FTD) comprises a group of neurodegenerative disorders that lead to progressive changes in language, behavior, personality, and movement. Accounting for approximately 60% of cases, the behavioral variant (bvFTD) represents the most common clinical presentation of FTD. MicroRNAs (miRNAs) are small non-coding RNAs involved in gene regulation and are expressed in various biological fluids. Considering bvFTD as an inflammatory disorder, this study investigated the expression of inflammation-related miRNAs in individuals with bvFTD compared with age- and sex-matched cognitively healthy controls.

Twenty patients with bvFTD and 20 cognitively healthy controls, matched for age and sex, were included in the study. Serum levels of miRNA-30c-5p and miRNA-125a-5p were analyzed.

miRNA-125a-5p expression was upregulated in individuals with bvFTD compared with controls (fold change = 2.02). No significant differences between groups were observed for miRNA-30c-5p. An inverse correlation was identified between miRNA-125a-5p expression and age within the bvFTD group. Pathway enrichment analysis revealed that miRNA-125a-5p was significantly involved in the regulation of genes associated with insulin receptor signaling, SUMOylation, SUMO E3 ligase-mediated protein modification, SUMOylation of chromatin organization proteins, estrogen-dependent gene expression, extracellular exosome pathways, neuron migration, microtubule dynamics, and nervous system development.

These findings suggest that miRNA-125a-5p may play an important role in FTD-related biological pathways, underscoring its potential as a molecular marker in the pathophysiology of this disorder.