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


Karabaş T., Sancar H., Şumnulu D., Ayaz L.

MOLECULAR BIOLOGY REPORTS, cilt.53, sa.1, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 53 Sayı: 1
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1007/s11033-026-11861-4
  • Dergi Adı: MOLECULAR BIOLOGY REPORTS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE
  • Trakya Üniversitesi Adresli: Evet

Özet

Background In this study, the neuroprotective potential of irisin was evaluated in an MPP+-induced SH-SY5Y in vitro Par-kinson's disease model through miRNA-associated changes related to the PGC-10/FNDC5/BDNF axis.
Material and Method An in vitro Parkinson's disease model was established by treating SH-SY5Y cells with 1500 & micro;M 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-AACt method.
Results FNDCS and BDNF levels were significantly decreased in the MPP group compared with the control group (p < 0.05). Conversely, PGC-la expression was significantly increased in both the irisin pre- and post-treatment groups. Com-pared with the MPP group, PGC-1a 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 sig-nificantly 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-10/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.