Male C57BL/6 mice wild-type (WT), 8 weeks of age, were from Chongqing Medical University, China. Mice were divided into four groups (n = 10-13 per group), control group, MPTP group, h-Trx-1 Tg group, and h-Trx-1 Tg + MPTP group. Control and h-Trx-1 Tg groups were administered saline only. For the Trx-1 knockdown experiment, mice were divided into six groups (n = 10-13 per group), control + saline group, control + MPTP group, AAV9-vehicle + saline group, AAV9-vehicle + MPTP group, AAV9-shRNA-mTrx-1 + saline group, and AAV9-shRNA-mTrx-1 + MPTP.

The AB strain of wild-type zebrafish (Danio rerio) was applied in this study. Zebrafish larvae at 4 dpf (days post-fertilization) were co-incubated with 250 uM 6-OHDA or 1.5 ug/mL nomifensine (Nomi, a dopamine transporter inhibitor) in 6-well plates at a density of 30 zebrafish embryos per group for 2 days and the medium was refreshed every day. The swimming total distance of each fish was recorded for 10 min and was analyzed by an automated video tracking system.

All animal maintenance and experiments were approved by The Ethical Committee of Guangzhou University of Chinese Medicine. A total of 36 SD rats (Sprague-Dawley; male; 230-260 g; 8-9-weeks old) were divided randomly into two study groups (n = 18 rats/group), i.e., the sham group (unilateral injection of the equal volume of saline) and model group (unilateral injection of 20 g of 6-OHDA). All surgical procedures were performed under (10 mg/kgxylazine, and 100 mg/kg ketamine, intraperitoneal administration) anesthesia using stereotactic apparatus (RWD, Shenzhen, China). The rats received either unilateral injections of 5 ul of 6-OHDA (Sigma-Aldrich, Germany; 4 ug/ul, dissolved in PBS) or 5 ul of saline into MFB (left medial forebrain bundle) at the rate of 1 ul/min. Injection coordinates were as follows (with reference to bregma): anteroposterior (A/P) = - 2.2 mm, lateral (LAT) = 1.5 mm, and dorsoventral (D/V) = 8.0 mm. The rats were placed in animal holding room (humidity: 50 ± 5%; temperature: 21 ± 1 ; 12-h dark/light cycle).

Fifty male C57BL/6 mice provided by Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China) resided in an animal house (temperature 26 ± 1 , humidity 50 ± 10%), in which the light was on for 12 h and off for 12 h. Mice were acclimatised for 1 week and allowed water and animal food with no limitations. Then, all mice were stochastically divided into 5 groups using random number tables available online (https://www.random-online.com/, accessed on 26 December 2021), including: (1) C group, a control group treated with normal saline for 7 consecutive days (n = 10); (2) M group, a model group with intraperitoneal injection of 20 mg/kg/day MPTP (Sigma-Aldrich, Taufkirchen, Germany, M0896) for 7 consecutive days (n = 10); (3) L group, treated with MPTP and 0.4 mg/kg/day liraglutide for 7 consecutive days (n = 10); (4) R group, treated with MPTP and 109 colony-forming unit (CFU) L. lactis MG1363 for 7 consecutive days via gavage (n = 10); (5) RG group, treated with MPTP and 109 CFUL. lactis MG1363-pMG36e-GLP-1 for 7 consecutive days via gavage (n = 10). All animals survived treatment and all animal experiments were administered from 9:00 to 12:00 in the morning to reduce systematic errors.

Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments.

In total, twelve healthy adult rhesus monkeys (Macaca mulatta lasiotis, aged 4-5 years, and weighed 3.5-5 kg at the start of the study) were obtained from Sichuan Primed Biological Technology Co., Ltd. Monkeys were randomly divided into two groups: normal (control) group (n = 3) and MPTP group (n = 9). Monkeys from MPTP group were administered with MPTP by intramuscular injection daily at the beginning of the study, and then the MPTP dose was gradually added to 0.5 mg/kg at the end of the experiment. Monkeys from control group were injected with saline instead, and the other conditions were the same with MPTP group.

In total, twelve healthy adult rhesus monkeys (Macaca mulatta lasiotis, aged 4-5 years, and weighed 3.5-5 kg at the start of the study) were obtained from Sichuan Primed Biological Technology Co., Ltd. Monkeys were randomly divided into two groups: normal (control) group (n = 3) and MPTP group (n = 9). Monkeys from MPTP group were administered with MPTP by intramuscular injection daily at the beginning of the study, and then the MPTP dose was gradually added to 0.5 mg/kg at the end of the experiment. Monkeys from control group were injected with saline instead, and the other conditions were the same with MPTP group.

Human a-synuclein (a-Syn) A53T overexpressiontransgenic mice(B6; C3-Tg (Prnp-SNCA*A53T) 83Vle/J) were originally obtained in breeding pairs from the Jackson Laboratory (004479) to generate a stable breeding colony. Animals were raised according to SPF level, kept at constant temperature (20 ± 2) , constant humidity (50 ± 10%), day and night cycle light (12-12 h), with free access to food and water.

Tumors were established by a subcutaneous injection of shRNA (control or DJ-1 KD) transfected H1299 cells (1,000,000/200 uL) into BALB/c female athymic nude mice (5 weeks, National Rodent Laboratory Animal Resource, Shanghai, China). Twelve days after injection, mice were randomly allocated into different groups and treated with vehicle (0.625% DMSO/99.375% HBSS (pH = 2)) or 30 mg/kg PE (tail intravenous injection, once every other day) for 16 days before the final tumor size was measured in all groups.

Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments.

Tumors were established by a subcutaneous injection of shRNA (control or DJ-1 KD) transfected H1299 cells (1,000,000/200 uL) into BALB/c female athymic nude mice (5 weeks, National Rodent Laboratory Animal Resource, Shanghai, China). Twelve days after injection, mice were randomly allocated into different groups and treated with vehicle (0.625% DMSO/99.375% HBSS (pH = 2)) or 30 mg/kg PE (tail intravenous injection, once every other day) for 16 days before the final tumor size was measured in all groups.

Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments.

Twenty male C57BL/6 mice at 12 weeks old were purchased from Hebei Medical University Experimental Animal Center. 10 mice of the experimental group were intraperitoneally injected with PQ (10 mg PQ (salt)/kg/dose) three times a week for 3 weeks according to the previous report. Ten mice of the control group were intraperitoneally injected with the same dose of normal saline. Once the experimental schedule was completed, firstly, the animals were used for behavioral tests. Then, the mice were anesthetized with 0.4% pentobarbital sodium (1 mL/100 g) solution and perfused. The substantia nigra tissue was exfoliated for subsequent experiments.

Fifty male C57BL/6 mice provided by Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China) resided in an animal house (temperature 26 ± 1 , humidity 50 ± 10%), in which the light was on for 12 h and off for 12 h. Mice were acclimatised for 1 week and allowed water and animal food with no limitations. Then, all mice were stochastically divided into 5 groups using random number tables available online (https://www.random-online.com/, accessed on 26 December 2021), including: (1) C group, a control group treated with normal saline for 7 consecutive days (n = 10); (2) M group, a model group with intraperitoneal injection of 20 mg/kg/day MPTP (Sigma-Aldrich, Taufkirchen, Germany, M0896) for 7 consecutive days (n = 10); (3) L group, treated with MPTP and 0.4 mg/kg/day liraglutide for 7 consecutive days (n = 10); (4) R group, treated with MPTP and 109 colony-forming unit (CFU) L. lactis MG1363 for 7 consecutive days via gavage (n = 10); (5) RG group, treated with MPTP and 109 CFUL. lactis MG1363-pMG36e-GLP-1 for 7 consecutive days via gavage (n = 10). All animals survived treatment and all animal experiments were administered from 9:00 to 12:00 in the morning to reduce systematic errors.

The AB strain of wild-type zebrafish (Danio rerio) was applied in this study. Zebrafish larvae at 4 dpf (days post-fertilization) were co-incubated with 250 uM 6-OHDA or 1.5 ug/mL nomifensine (Nomi, a dopamine transporter inhibitor) in 6-well plates at a density of 30 zebrafish embryos per group for 2 days and the medium was refreshed every day. The swimming total distance of each fish was recorded for 10 min and was analyzed by an automated video tracking system.

Fifty male C57BL/6 mice provided by Hunan SJA Laboratory Animal Co., Ltd. (Changsha, China) resided in an animal house (temperature 26 ± 1 , humidity 50 ± 10%), in which the light was on for 12 h and off for 12 h. Mice were acclimatised for 1 week and allowed water and animal food with no limitations. Then, all mice were stochastically divided into 5 groups using random number tables available online (https://www.random-online.com/, accessed on 26 December 2021), including: (1) C group, a control group treated with normal saline for 7 consecutive days (n = 10); (2) M group, a model group with intraperitoneal injection of 20 mg/kg/day MPTP (Sigma-Aldrich, Taufkirchen, Germany, M0896) for 7 consecutive days (n = 10); (3) L group, treated with MPTP and 0.4 mg/kg/day liraglutide for 7 consecutive days (n = 10); (4) R group, treated with MPTP and 109 colony-forming unit (CFU) L. lactis MG1363 for 7 consecutive days via gavage (n = 10); (5) RG group, treated with MPTP and 109 CFUL. lactis MG1363-pMG36e-GLP-1 for 7 consecutive days via gavage (n = 10). All animals survived treatment and all animal experiments were administered from 9:00 to 12:00 in the morning to reduce systematic errors.

A total of 48 male Sprague-Dawley rats (weighing, 180-220 g; 6-8 weeks of age) were purchased from the Animal Center of Guangzhou University of Chinese Medicine (Guangzhou, China). The rats were anesthetized (100 mg/kg ketamine and 10 mg/kg xylazine, intraperitoneal injection) and placed in a stereotaxic apparatus with the skull flat. An intracerebral injection of 6-OHDA was performed at 2 sites in the right SN pars compacta (SNpc) and ventral tegmental area (VTA): Anteroposterior (A/P)=-4.9 mm; mediolateral (M/L)=-1.9 mm; dorsoventral (D/V)=-7.5 mm; and anteroposterior (A/P)=-4.9 mm; mediolateral (M/L)=-1.1 mm; dorsoventral (D/V)=8.0 mm. During the surgery, body temperature was maintained at ~36.5 using a heating pad. All rats received meticulous post-operative care.