Fig. 6

Hbβ is necessary for the action of KDS12025. a Representative superresolution microscopy image showing Hbβ expression and gene silencing in cultured astrocytes transfected with the AAV-Hbβ-shRNA or AAV-Sc-shRNA vector. b Quantification of Hbβ expression specifically in DAPI-negative nucleolus regions in Sc- and Hbβ-shRNA-transfected astrocytes. c Relative levels of ROS, including H₂O₂, in Sc- or Hbβ-shRNA-transfected astrocytes treated with vehicle, Aβ, or Aβ + KDS12025 (10 μM). The “#” symbol (red) indicates differences in Aβ-induced H₂O₂ between Sc-shRNA and Hbβ-shRNA (n values indicate the number of wells). d Continuous live-cell H₂O₂ imaging using oROS-G in response to Aβ (5 μM) treatment, with KDS12025 (0.1, 1, or 10 μM) in Sc- or Hbβ-shRNA. e Comparison of oROS-G intensity between the Sc-shRNA and Hbβ-shRNA groups with KDS treatment (n indicates the number of cells). f Schematic timeline of the injection of AAV-pSicoR-Hbβ (or Sc)-shRNA into the CA1 hippocampus of APP/PS1 mice. g Discrimination index in the NPR test across the groups (n = 6 mice per group). h Quantification of Hbβ intensity in GFAP-positive areas (n indicates cell numbers; 3 mice per group; representative images in Supplementary Fig. 16). Quantification of the GFAP-positive area (i) and GFAP intensity (j). k Schematic timeline of the injection of AAV-pSico-Hbβ (or Sc)-shRNA combined with AAV-GFAP- (or CaMKII-) Cre virus into the CA1 hippocampus of APP/PS1 mice. l Discrimination index from the NPR test across the groups (n = 4 mice per group, CaMKII; n = 3). m Quantification of Hbβ intensity in GFAP-positive areas (n indicates cell numbers; 3 mice per group; representative images in Supplementary Fig. 17). GFAP-positive area (n) and GFAP intensity (o) quantification. p Schematic timeline of the injection of AAV-pSico-Hbβ (or Sc)-shRNA combined with AAV-GFAP- (or CaMKII-) Cre virus into the SNpc of A53T mice. q Schematic diagram of the rotarod test and latency-to-fall test of A53T+Sc::GFAP, A53T+Sc::GFAP + KDS, A53T+Sh::GFAP + KDS, and A53T+Sh::CaMKII+KDS mice. r, s Quantification of the GFAP-positive area and number of TH-positive neurons per hemisphere in the SNpc (representative images in Supplementary Fig. 18). The data are presented as the means ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001; ns not significant. Additional statistics are provided in Supplementary Table 8