Fig. 6: Alpha-lipoic acid decreases lipid peroxidation and phosphorylated α-synuclein in CHCHD2-deficient dopaminergic neurons.

A The levels of mitochondrial α-KG of CHCHD2 knockout HEK293T cells (KO #1) treated with vehicle or 50 μM α-lipoic acid (α-LA). N = 4 biological replicates. Data shown are mean ± SEM. Two-sided t test. B Representative images of oxidized and reduced C11-BODIPY signals of CHCHD2-deficient dopaminergic neurons at baseline (DMSO condition) and RSL3-induced conditions pretreated with serial concentrations of α-LA. Scale bar, 20 μm. N = 4 independent experiments. C The ratio of oxidized to reduced C11-BODIPY fluorescence intensities of CHCHD2-deficient dopaminergic neurons at baseline (DMSO condition) and RSL3-induced conditions pretreated with serial concentrations of α-LA. Images were collected and analyzed from N = 4 independent experiments. Data shown are mean ± SEM. One-way ANOVA with Dunnett’s test. D Immunoblots and quantifications of pS129 α-synuclein (α-Syn) levels in striatum of 24-month-old wildtype and Chchd2 T61I knock-in mice. n = 3 mice. Data shown are mean ± SEM. Two-sided t test. E Immunoblots and quantifications of pS129 α-synuclein levels in DA neurons derived from T61I/ + PD patient and isogenic control iPSCs. N = 3 biological replicates. Data shown are mean ± SEM. Two-sided t test. F, G Immunoblots and quantifications of pS129 α-synuclein levels of control and CHCHD2-deficient human DA neurons. N = 6 biological replicates. Data shown are mean ± SEM. Two-sided t test. Immunoblots and quantifications of pS129 α-synuclein levels in RIPA- soluble (H) and insoluble (I) fractions of CHCHD2-deficient human DA neurons treated with vehicle, 50 μM or 100 μM α-LA. CBB, Coomassie brilliant blue. N = 3 biological replicates. Data shown are mean ± SEM. One-way ANOVA with Dunnett’s test. Source data are provided as a Source Data file.