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<p>Parkinson’s disease (PD) is a progressive neurodegenerative disease, which can’t be cured at present. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomal microRNAs are involved in various neurodegenerative diseases. While BMSC-derived exosomes show therapeutic potential in PD, their specific mechanisms remain elusive. This research aims to elucidate the functional mechanism of exosomal miR-1278 from BMSCs in PD. The motor deficits and cognitive function of mice were assessed by Pole test, Rotarod test, Open field test, and Morris water maze. Western blotting assay and qRT-PCR were carried out to evaluate gene and miRNA expressions. Neuronal apoptosis was elevated by TUNEL assay. Immunofluorescence staining assessed microglial activation. Flow cytometry assay was conducted to detect microglia apoptosis and polarization. Inflammatory cytokines levels were measured by ELISA. Metabolic assays included Seahorse ECAR/OCR, FAO, and lactic acid quantification. BMSCs can improve the motor and cognitive deficits of PD mice by relieving neuronal damage and microglia-induced neuroinflammation. As for the molecular mechanism, downregulation of miR-1278 was identified in plasma exosomes and BMSCs from PD patients. And exosomes can transfer miR-1278 from BMSCs to microglia. Exosomal miR-1278 alleviated apoptosis and M1 polarization of microglia. Further, miR-1278 targets LDHA and downregulates its expression microglia. LDHA knockdown promoted M2 polarization and prevented apoptosis of microglia by impairing glycolysis and enhancing fatty acid oxidation (FAO). In vivo assay also demonstrated that BMSCs-derived miR-1278 relieved motor and cognitive deficits in PD mice through regulating LDHA-mediated polarization of microglia. Exosomal miR-1278 from BMSCs promotes M2 polarization of microglia by regulating LDHA-mediated metabolism reprogramming, thereby relieving neuronal damage and neuroinflammation in PD. This study elucidates a novel mechanistic pathway involving miR-1278/LDHA, offering a precise target for future PD therapies.</p>

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Exosomal miR-1278 From Bone Marrow Mesenchymal Stem Cells Modulates Ldha-Mediated Microglia Polarization to Decelerate Parkinson’s Disease Pathology

  • 期刊论文

  • 发表日期：

    2026年4月23日

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  • Wenci Yan,
  • Shuainan Ma,
  • Ruyue Liu,
  • Chang Liu,
  • Chunyan Wang

摘要

Parkinson’s disease (PD) is a progressive neurodegenerative disease, which can’t be cured at present. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomal microRNAs are involved in various neurodegenerative diseases. While BMSC-derived exosomes show therapeutic potential in PD, their specific mechanisms remain elusive. This research aims to elucidate the functional mechanism of exosomal miR-1278 from BMSCs in PD. The motor deficits and cognitive function of mice were assessed by Pole test, Rotarod test, Open field test, and Morris water maze. Western blotting assay and qRT-PCR were carried out to evaluate gene and miRNA expressions. Neuronal apoptosis was elevated by TUNEL assay. Immunofluorescence staining assessed microglial activation. Flow cytometry assay was conducted to detect microglia apoptosis and polarization. Inflammatory cytokines levels were measured by ELISA. Metabolic assays included Seahorse ECAR/OCR, FAO, and lactic acid quantification. BMSCs can improve the motor and cognitive deficits of PD mice by relieving neuronal damage and microglia-induced neuroinflammation. As for the molecular mechanism, downregulation of miR-1278 was identified in plasma exosomes and BMSCs from PD patients. And exosomes can transfer miR-1278 from BMSCs to microglia. Exosomal miR-1278 alleviated apoptosis and M1 polarization of microglia. Further, miR-1278 targets LDHA and downregulates its expression microglia. LDHA knockdown promoted M2 polarization and prevented apoptosis of microglia by impairing glycolysis and enhancing fatty acid oxidation (FAO). In vivo assay also demonstrated that BMSCs-derived miR-1278 relieved motor and cognitive deficits in PD mice through regulating LDHA-mediated polarization of microglia. Exosomal miR-1278 from BMSCs promotes M2 polarization of microglia by regulating LDHA-mediated metabolism reprogramming, thereby relieving neuronal damage and neuroinflammation in PD. This study elucidates a novel mechanistic pathway involving miR-1278/LDHA, offering a precise target for future PD therapies.