2. Academic Validation
  3. GSDMD-Deficient G-MDSCs Exert Profoundly Suppressive Activity to Relieve MPTP-Induced Parkinson's Disease

GSDMD-Deficient G-MDSCs Exert Profoundly Suppressive Activity to Relieve MPTP-Induced Parkinson's Disease

  • CNS Neurosci Ther. 2025 Oct;31(10):e70626. doi: 10.1111/cns.70626.
Qi Wu 1,  Fangzhou Liu 1,  Min Gu 1,  Junjie Wei 1,  Guotao Lu 2,  Li Qian 1,  Xiaobo Li 3,  Weijuan Gong 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou, China.
  • 2 Department of Gastroenterology, Affiliated Hospital, Yangzhou University, Yangzhou University, Yangzhou, China.
  • 3 Department of Neurology, Affiliated Subei People's Hospital, Yangzhou University, Yangzhou, China.
  • 4 Univeristy Key Laboratory of Jiangsu Province for Nucleic Acid & Cell Fate Regulation (Yangzhou University), Yangzhou, China.
PMID: 41084350 DOI: 10.1111/cns.70626
Abstract

Aims: Myeloid-derived suppressor cells (MDSCs) are elevated in Parkinson's disease (PD), but their functional role remains unclear. This study investigated whether GSDMD deficiency enhances the immunosuppressive activity of granulocytic MDSCs (G-MDSCs) to mitigate PD progression.

Methods: Flow cytometry and Western blot analyzed G/M-MDSCs in 37 PD patients and 21 controls. An MPTP-induced PD mouse model was used to assess GSDMD-deficient G-MDSCs through behavioral tests, immunohistochemistry, and adoptive transfer experiments. The NLRP3 Inhibitor ACT001 was evaluated for therapeutic potential.

Results: PD patients and MPTP-treated mice showed increased peripheral G-MDSCs with reduced NLRP3/GSDMD activation. GSDMD knockout mice exhibited attenuated PD symptoms, reversed by MDSCs depletion. Adoptive transfer of GSDMD-deficient G-MDSCs suppressed microglial activation and improved motor function. ACT001 enhanced G-MDSCs immunosuppression and alleviated PD pathology.

Conclusion: GSDMD deficiency promotes immunosuppressive G-MDSCs that inhibit neuroinflammation and PD progression. Targeting GSDMD to modulate MDSCs' function represents a novel therapeutic strategy for PD.

Keywords

ACT001; GSDMD; G‐MDSCs; MPTP; Parkinson's disease.

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