Effect of irisin on miRNA-associated changes in the PGC-1α/FNDC5/BDNF Axis in an in vitro model of MPP⁺-induced Parkinson's disease.

BACKGROUND: In this study, the neuroprotective potential of irisin was evaluated in an MPP⁺-induced SH-SY5Y in vitro Parkinson’s disease model through miRNA-associated changes related to the PGC-1α/FNDC5/BDNF axis. MATERIAL AND METHOD: An in vitro Parkinson’s disease model was established by treating SH-SY5Y cells with 1500 μM MPP⁺ for 24 h. A non-cytotoxic irisin concentration (20 nM) was determined via using the MTT assay. Cells were divided into control, MPP⁺, irisin pre-treatment, and post-treatment groups. miRNA and mRNA expression levels were quantified by qRT-PCR and analyzed using the 2⁻ΔΔCt method. RESULTS: FNDC5 and BDNF levels were significantly decreased in the MPP⁺ group compared with the control group (p < 0.05). Conversely, PGC-1α expression was significantly increased in both the irisin pre- and post-treatment groups. Compared with the MPP⁺ group, PGC-1α expression was significantly elevated under both treatment conditions, while FNDC5 expression showed a significant increase, particularly in the pre-treatment group. miRNA analysis revealed a significant downregulation of miR-129-1-3p and miR-143-3p in the MPP⁺ group compared to the control. Irisin pre-treatment significantly increased miR-143-3p and miR-182-5p levels, whereas post-treatment significantly elevated miR-129-1-3p, miR-138-5p, and miR-182-5p expression, compared with the control group. Compared with the MPP⁺ group, miR-129-1-3p and miR-182-5p were upregulated in both treatment groups; whereas miR-143-3p increased predominantly in the pre-treatment group, and miR-138-5p showed a significant increase only in the post-treatment condition. CONCLUSION: These findings demonstrate that irisin influences the PGC-1α/FNDC5/BDNF axis and selected miRNAs in an MPP⁺-induced in vitro Parkinson's disease model. The observed results indicate an association between irisin treatment and miRNA expression changes rather than a direct miRNA-mediated regulatory mechanism. Further functional studies are required to establish causal relationships and validate the predicted miRNA–target interactions.