The paper shows that circ-find-0001774 sponges miR-153-3p to boost Wnt/β-catenin signaling, lowering autophagy/apoptosis and improving dopaminergic neuron survival and motor behavior in MPP+/MPTP PD models.

Provides a mechanistically actionable circRNA–miRNA–Wnt/β‑catenin axis with in vivo neuroprotective effects that could inform novel therapeutic strategies, although human relevance and delivery/translation hurdles remain.

OBJECTIVE: This study aimed to investigate how circ-find-0001774 regulates miR-153-3p in Parkinson’s disease (PD). METHODS: We first validated the targeting relationship between circ-find-0001774 and miR-153-3p using dual-luciferase reporter assays, excluding any association with let-7a-5p. Next, we constructed a circ-find-0001774 overexpression vector and transfected it into MN9D dopaminergic neurons, confirming transfection efficiency by qPCR. In vitro, we induced a PD cell model with 100 µmol/L MPP+ iodide for 24 h and assessed cell proliferation using CCK-8, apoptosis via flow cytometry, and miR-153-3p and LC3Ⅱ/Ⅰ protein levels by qPCR and Western blotting. In vivo, we established a mouse PD model by daily intraperitoneal injection of 18 mg/kg MPTP for seven days, evaluating motor function through behavioral tests, observing brain pathology via HE staining, and analyzing miR-153-3p and β-catenin protein levels by qPCR and Western blotting. RESULTS: Dual-luciferase assays confirmed a specific targeting interaction between miR-153-3p and circ-find-0001774. In vitro, circ-find-0001774 overexpression significantly enhanced cell proliferation, reduced apoptosis and decreased miR-153-3p and LC3Ⅱ/Ⅰ protein expression levels. In vivo, circ-find-0001774 overexpression notably ameliorated motor deficits in the mouse PD model mitigated neurodegeneration, decreased miR-153-3p level and increased β-catenin protein expression levels. CONCLUSION: Our study reveals that circ-find-0001774 modulates miR-153-3p, mainly through the Wnt/β-Catenin signaling pathway, suggesting its therapeutic potential for PD. These findings provide novel insights and experimental foundations for further developing PD treatment strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12031-026-02509-w.