Ultimately, this SIX2-initiated cascade rescued neuronal apoptosis and restored motor coordination in both cellular and animal models of PD.<h4>Conclusion</h4>SIX2 promotes microglial M2 polarization via the DDIT4/mTOR/autophagy axis and mediates neuroprotection through exosomal miR-3470b targeting of GREM1/TGF-β signaling, revealing novel therapeutic targets for PD immunotherapy. The gene discussed is DDIT4; the disease is Parkinson disease.