Fig. 5: Withaferin A suppresses STING to protect dopaminergic neurons from MPTP neurotoxicity.

A Representative TH staining of SNc dopaminergic neurons in DMXAA or vehicle-treated mice, scale bar, 400 μm. B Unbiased stereological counts of TH⁺ neurons in SNc of DMXAA or vehicle-treated mice. Data are mean ± s.e.m.; n = 10 biologically independent animals; *P < 0.05 and **P < 0.01 by two-way ANOVAs followed by Tukey’s multiple comparisons test. C Representative Iba1 and STING immunostaining in SNc of DMXAA or vehicle-treated mice, scale bar, 200 μm. D Quantification of Iba1 and STING levels. Data are mean ± s.e.m.; n = 10 biologically independent animals; *P < 0.05, **P < 0.01, and ***P < 0.001 by two-way ANOVAs followed by Tukey’s multiple comparisons test. E Time to traverse beam apparatus, time to descend pole, hind-limb clasping reflex score, fall latency from an accelerating rotarod and gait analysis. Data are mean ± s.e.m.; n = 9 biologically independent animals; *P < 0.05, **P < 0.01, and ***P < 0.001 by two-way ANOVAs followed by Tukey’s multiple comparisons test. F Representative TH, GFAP, Iba1 and Nissl staining of SNc in WT and STING^gt/gt mice, scale bar, 400 μm. G Unbiased stereological counts of TH⁺, GFAP⁺, Iba1⁺ and Nissl⁺ cells in SNc of WT and STING^gt/gt mice. Data are mean ± s.e.m^.; n = 9 biologically independent animals; *P < 0.05, **P < 0.01, and ***P < 0.001 by two-way ANOVAs followed by Tukey’s multiple comparisons test. H Representative immunoblots and quantification of TH and STING in SNc of DMXAA treated mice (cropped blot images are shown, see Supplementary Fig. 16 for full immunoblots). I Representative gait test images measured in WT and STING^gt/gt mice; n = 9 biologically independent animals. J Representative immunoblots and quantification of TH, DJ1, Nrf2 in SNc of WT and STING^gt/gt mice (cropped blot images are shown, see Supplementary Fig. 16 for full immunoblots). Data are mean ± s.e.m.; n = 9 biologically independent animals; *P < 0.05, **P < 0.01, and ***P < 0.001 by two-way ANOVAs followed by Tukey’s multiple comparisons test. K Relative mRNA expression in SNc of WT and STING^gt/gt mice. Data are mean ± s.e.m.; n = 6 biologically independent animals. L Time to traverse beam apparatus, time to descend pole, hind-limb clasping reflex score, fall latency from an accelerating rotarod. Data are mean ± s.e.m.; n = 10 biologically independent animals; *P < 0.05, **P < 0.01, and ***P < 0.001 by two-way ANOVAs followed by Tukey’s multiple comparisons test. M Schematic summary of the mechanism underlying the neuroprotective actions of WA in PD.