Abstract

Parkinson’s disease (PD) is a frequently occurring neurodegenerative condition.This study aimed to explore the expression, diagnostic value, and regulatory mechanism of serum miR-338-5p in PD. Serum miR-338-5p and LRP1 levels were measured by RT-qPCR in 62 PD patients and 84 healthy controls. MRI parameters including substantia nigra (SN) volume, quantitative susceptibility mapping (QSM), and diffusion tensor imaging metrics were obtained. Diagnostic performance was assessed by receiver operating characteristic (ROC) analysis. Multivariate logistic regression identified independent risk factors. SH-SY5Y cells treated with MPP⁺ served as a cellular PD model to evaluate the effects of miR-338-5p overexpression on α-synuclein aggregation, tyrosine hydroxylase expression, and cell viability. Bioinformatics analysis and dual-luciferase reporter assays validated LRP1 as a target of miR-338-5p. The results showed that serum miR‑338‑5p levels were significantly decreased, while LRP1 levels were increased in PD patients, with a negative correlation between them. MRI revealed reduced SN volume, SNc hyperintensity area, fractional anisotropy (FA), and N‑acetylaspartate/creatine (NAA/Cr), as well as elevated mean diffusivity (MD) and QSM in the PD group. The combination of miR‑338‑5p and multi‑parameter MRI improved diagnostic performance, with an area under the receiver operating characteristic curve (AUC) of 0.919. Multivariate logistic regression indicated that downregulation of miR‑338‑5p was an independent risk factors for PD. In vitro, overexpression of miR‑338‑5p suppressed α‑syn expression, restored TH levels, and improved cell viability in MPP⁺‑injured SH‑SY5Y cells. Dual‑luciferase assay confirmed LRP1 as a direct target of miR‑338‑5p, and LRP1 overexpression reversed the neuroprotective effects of miR‑338‑5p. These findings suggest that serum miR‑338‑5p combined with MRI multi‑parameters shows promising diagnostic value for PD, and miR‑338‑5p may exert neuroprotecti