2. Academic Validation
  3. Activation of mitophagy via miR-223/NLRP3 axis ameliorates dopaminergic neuronal damage in parkinson's disease

Activation of mitophagy via miR-223/NLRP3 axis ameliorates dopaminergic neuronal damage in parkinson's disease

  • Metab Brain Dis. 2026 Mar 23;41(1):65. doi: 10.1007/s11011-026-01805-z.
Yan Wu 1,  Xuemei Fan 2,  Dewei Wang 1,  Hui Yang 3
Affiliations

Affiliations

  • 1 Department of Rehabilitation, Hangzhou Geriatric Hospital, Affiliated Hangzhou First People's Hospital Chengbei Campus, Westlake University, School of Medicine, Hangzhou, China.
  • 2 Department of Neurology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, No. 261, Huansha Road, Shangcheng District, Hangzhou, Zhejiang Province, 310006, China.
  • 3 Department of Neurology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, No. 261, Huansha Road, Shangcheng District, Hangzhou, Zhejiang Province, 310006, China. [email protected].
PMID: 41870730 DOI: 10.1007/s11011-026-01805-z
Abstract

Parkinson’s disease (PD) is a major neurodegenerative disorder. MiR-223 as a potential biomarker for Parkinson’s disease, NLRP3-driven neuroinflammation, and their interaction represent a significant research gap. This study aimed to investigate the role of Mitophagy activation by targeting miR-223/NLRP3 interaction to alleviate dopamine neuronal damage in PD. Firstly, in vivo, rats were divided into sham, PD model, and intervention groups (PD + agomiR-NC or PD + agomiR-223). AgomiRs were delivered via targeted intracranial injection. Neurobehavioral assessments, histopathological analysis, mitochondrial ultrastructure quantification, and neuroinflammatory marker detection were performed to evaluate PD progression and Mitophagy. Second, in vitro, MPTP-treated PC12 cells were divided into seven groups and transfected with either miR-223 mimic, mimic negative control (NC), oe-NLRP3, or oe-NC. MiR-223 and NLRP3 expression, cell viability, mitochondrial morphology/function, and inflammatory responses were analyzed to elucidate the molecular mechanisms linking miR-223/NLRP3 signaling to Mitophagy activation. First, in vivo experiments demonstrated that PD + agomiR-223 rats exhibited significant improvements in motor performance, improved motor function and exploratory behavior, attenuated histopathological brain damage, and preserved mitochondrial ultrastructure compared to the PD group. Additionally, agomiR-223 treatment markedly decreased neuroinflammatory markers in brain tissues. Then, in vitro experiments showed that after miR223 mimic treatment, PC12 cell viability, Mitophagy level and inflammation level were improved compared with MPTP group, while oe-NLRP3 addition offset these effects. Additionally, Autophagy activator, rapamycin, reversed the impact of oe-NLRP3 on MPTP+ miR223 mimic treated cells. These findings suggest miR-223 alleviates dopaminergic neuronal damage in PD by inhibiting NLRP3 inflammasome activation and promoting Mitophagy.

Keywords

Dopamine neuronal damage; MiR-223; Mitophagy; NLRP3; Parkinson's disease.

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