Upregulation of miR-361-5p attenuates MPP+-induced neurotoxicity in dopaminergic SH-SY5Y cells as Parkinson's disease model

Programmed cell death plays a crucial role in the pathogenesis of Parkinson's disease, yet the involvement of microRNAs (miRNAs) in this process remains inadequately understood. Previous studies have indicated a decreased expression pattern of hsa-miR-361-5p in patients with neurodegenerative diseases and in cell models of these conditions. This study aimed to predict the target genes of hsa-miR-361-5p, and to validate the predicted interactions at the mRNA level between hsa-miR-361-5p and its predicted target genes. In addition, we investigated the potential neuroprotective effect of miR-361-5p by assessing its effects on apoptosis and cell viability in SHSY-5Y cells using MTS assay and flow cytometry. Notably, overexpression of miR-361-5p significantly attenuated MPP⁺-induced neurotoxicity. Utilizing bioinformatics and dual-luciferase reporter assays, heme oxygenase 1 (HMOX1) and Fas associated via death domain (FADD) were identified as direct targets of miR-361-5p. Moreover, overexpression of miR-361-5p led to a decrease in the expression of HMOX1 and FADD genes, both known to be involved in cell death processes such as apoptosis and ferroptosis. Our findings indicate that miR-361-5p regulates the expression of HMOX1 and FADD, suggesting that miR-361-5p may represent a potential therapeutic target in Parkinson's disease.