CUR administration prevented motor impairments, dopaminergic neuronal loss and α-synuclein aggregation in MPTP-induced PD mice. Male C57BL/6 mice were received intragastric administration of CUR (25,100,400 mg/kg) once a day for 4 weeks. On day 15, mice were treated with 200 μL saline containing MPTP (30 mg/kg) or 200 μL saline via intraperitoneal injection every day for a total of 5 times to establish PD mice model. On day 28, behavioral tests were performed to evaluate the motor function and the mice were sacrificed to determine the pathology of PD by immunohistochemistry, immunofluorescence and immunoblot. (A) The molecular structure of CUR. (B) The experimental design of CUR intervention in MPTP-induced PD mice. (C, D) Representative traces and quantification of the open field test among MPTP treated mice, CUR treated mice and controls (n = 10). Bluepoint: starting position; Redpoint: ending position. (E, F) Quantification of performance in the pole test and the rotarod test among 5 groups (n = 10). (G) Representative immunofluorescence (upper) and immunohistochemistry (lower) images of TH-positive fibers and neurons in the striatum and SNpc among 5 groups. (H) Quantification of TH-positive fibers and neurons in the striatum and SNpc (n = 5). (I) Representative bands of TH protein in striatum of one hemisphere determined by WB and quantification of TH expression among 5 groups (n = 3). (J) Representative thioflavin-S staining images of α-syn-positive aggregations in the SNpc. (K) Quantification of the percentage of thioflavin-S stained area in the SNpc among MPTP treated mice, CUR (100 mg/kg) treated mice and controls (n = 3). (L, M) Representative bands of α-syn protein in striatum of one hemisphere determined by WB and quantification of α-syn expression among MPTP treated mice, CUR (100 mg/kg) treated mice and controls (n = 3). (N) Representative immunofluorescence images of pSer129α-syn-positive cells in the striatum and SNpc among 3 groups. (O) Quantification of pSer129α-syn-positive cells in the striatum and SNpc among 3 groups (n = 5). Data are expressed as mean ± SEM and representative results are one of the independent experiments. All statistical differences were tested using one-way ANOVA in (C–E, F, G, I, K, M, O). Quantification of TH-positive fibers and neurons, α-syn-positive area, pSer129-α-syn-positive cells was performed by ImageJ. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.