(A) Schematic diagram showing the study design using 8-month-old A53T transgenic mice treated with low-dose sorafenib (Sora) before measurements. Disordered motor coordination of A53T mice was accelerated by Sora, while the WT mice were unaffected, as displayed by behavioral tests (B) rotarod, (C) pole climbing and (D and E) Catwalk gait analysis (n = 8 mice each group). (F) IHC of coronal brain sections labeled with TH antibody and hematoxylin (left, scale bar: 2 mm). The substantia nigra (dotted area) were amplified on right, scale bar: 500 μm. (G) Western blotting (top) and quantitative analysis (bottom) of TH expression in midbrain. The contents of (H) GSH and (I) MDA were measured in midbrain. (J) Western blotting (left) and quantitative analysis (right) of 4-HNE expression in midbrain. Data of oxidized phospholipids were extracted and displayed as (L) PCA and (K) volcano plots showing the fold changes (X-axis) versus significance (Y-axis) by t-test. (M) Ferroptosis-related genes were detected by quantitative real-time PCR assay and relative expressions displayed as a heatmap. (N) Western blotting (upper) and quantitative analysis (bottom) of GPX4 expression in midbrain (n = 6 mice each group). All data represent mean ± SEM. *P < 0.05, **P < 0.01 and ***P < 0.001, by 1-way ANOVA with Dunnett T3 (for B, C, E, and H) or Bonferroni’s posthoc (for G, I, J, and N) test.