|
Fig. 7 ACLY inhibition rescues α-Syn-induced pathology in SNCA mouse model (A) Schematic of the study paradigm, including the intracerebroventricular (ICV) infusion by minipump and designated collection time points. (B) p300 localization, mTORC1, and autophagy levels in the brains of SNCA mice after injection with 100 mM HC for 28 days. n = 6 each group, two-tailed unpaired t test. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 vs. vehicle-injected SNCA mice. (C) Rescue of AMPK activity after injection with 100 mM HC for 28 days. n = 6 each group, two-tailed unpaired t test. ∗p < 0.05 vs. vehicle-injected SNCA mice. (D) Decreased total human α-Syn level after injection with 100 mM HC for 28 days. n = 8 for HC-treated and n = 9 for vehicle control group, two-tailed unpaired t test. ∗∗p < 0.01 vs. vehicle-injected SNCA mice. Scale bar, 20 and 10 μm (enlarged images). Arrowheads indicate human α-Syn signals. (E) Decreased phosphorylated α-Syn at Ser129 after injection with 100 mM HC for 28 days. n = 8 for HC-treated and n = 9 for vehicle control group, two-tailed unpaired t test. ∗p < 0.05 vs. vehicle-injected SNCA mice. Scale bar, 20 and 10 μm (enlarged images). (F) Decreased aggregated α-Syn level after injection with 100 mM HC for 28 days. n = 8 for HC-treated and n = 9 for vehicle control group, two-tailed unpaired t test. ∗∗∗p < 0.001 vs. vehicle-injected SNCA mice. Scale bar, 20 and 10 μm (enlarged images). Arrowheads indicate α-Syn aggregates signals. (G) Reduced γ-H2AX level after injection with 100 mM HC for 28 days. n = 6 each group, two-tailed unpaired t test. ∗p < 0.05 vs. vehicle-injected SNCA mice. (H) Rescue of TH expression in the striatum after injection with 100 mM HC for 28 days. Representative confocal micrographs (maximum intensity projection) and quantification of TH signal (red) in striatal brain slices derived from SNCA mice. Nuclei were counterstained with DAPI. n = 8 for both HC-treated and vehicle control group, n = 4 for WT mice. One-tailed unpaired t test. ∗p < 0.05. Scale bar, 20 μm. (I) Schematic diagram of this study. Data are presented as mean values ± SEM unless otherwise specified. See also Figure S7.