Table 1.

Characteristics of animal studies that analyze the impact of SEM in PD.

Article	Animals/ Cells	Study Design (Randomization, Blind)	Pathology Model	Biochemical Tests	Behavior Tests	SEM (dose, Administration, Period of Time)	Other Drugs
Poupon-Bejuit 2022 [97]	Mice	Randomized, double-blind	Pla2g6−/− transgenic mice	-Hematoxylin/eosin staining -PAS staining. -Immunohistochemistry: CD68, NeuN, GFAP, Iba-1. -Western blot: RIP1, RIP3, β-actin. -PCR: GLP-1R gene, ATF-3, BCl2, BClxL Bax. -Stereology: pan-neuronal marker NeuN. -Blood analysis: total white blood cell count, neutrophils, lymphocytes, monocytes, eosinophils and basophils count, hematocrit, platelets, red blood cells, hemoglobin, and mean corpuscular volume.	Open field Rotarod Vertical pole	0.5, 0.25, 0.15 μg/g, i.p. injected once a week until the end of the experiment	No
Zhang 2018 [32]	Mice	Randomized	MPTP 20 mg/kg i.p. once daily for 7 days	-Immunohistochemistry: TH, GFAP, Iba-1, 4-HNE, BCl2, Bax. -Western blot: BCl2, Bax, β-actin, ATC7, LC2, Beclin1, SQSTM1, P62.	Open field Rotarod Footprint	25 nmol/kg, i.p., once daily for 7 days	Liraglutide 25 nmol/kg i.p. once daily for 7 days
Zhang 2019 [103]	Mice	In vivo, randomized	MPTP 20 mg/kg i.p. once daily for 30 days	-Immunohistochemistry: TH, GFAP, Iba-1, 4-HNE. -Western blot: BCl2, Bax, β-actin, α-Syn, ATC7, LC3, Beclin1, SQSTM1, GDNF.	Open field Rotarod Footprint gait Grip strength	25 nmol/kg, i.p., once daily for 30 days	Liraglutide 25 nmol/kg i.p. once daily for 30 days
Zhang 2022 [20]	Rats	Randomized, blind	6-OHDA	-ELISA: DA, TNF-α, IL-1β. -Western blot: TH, α-syn, IRS-1, IRS-1(phospho-S312), β-actin, GAPDH. -Immunofluorescence: TH.	Apomorphine Rotation	25 nmol/kg, i.p., once daily for 30 days postlesion	DA5-CH 25 nmol/kg, i.p., once daily for 30 days postlesion
Liu 2022 [23]	SH-SY5Y cells	In vitro	6-OHDA	-MTT method. -Western blot: LC3II, LC3I, Beclin1, P62, β-actin, ATG7. -Flow cytometry: measurement of ROS levels, membrane potential.	Not applicable	0, 1, 10, 100 nmol/L semaglutide	Liraglutide 0, 1, 10, 100 nmol/L

Abbreviations: Pla2g6−/−—Phospholipase A2, group VI knockout (a genetic modification where the Pla2g6 gene is knocked out), PAS—Periodic Acid-Schiff stain (a staining method used to detect glycogen and other carbohydrates), CD68—Cluster of differentiation 68 (a marker for macrophages and monocytes), NeuN—Neuronal Nuclei (a neuron-specific nuclear protein), GFAP—glial fibrillary acidic protein (a marker for astrocytes), Iba-1—Ionized calcium-binding adapter molecule 1 (a marker for microglia), RIP1—Receptor-interacting protein 1, RIP3—rRceptor-interacting protein 3, β-actin—Beta-actin (a cytoskeletal protein often used as a loading control in Western blots), PCR—Polymerase chain reaction, GLP-1R gene—Glucagon-like peptide-1 receptor gene, ATF-3—activating transcription Factor 3, BCl2—B-cell lymphoma 2 (anti-apoptotic protein), BClxL—B-cell lymphoma-extra large (anti-apoptotic protein), Bax—Bcl-2-associated X protein (pro-apoptotic protein), MPTP—1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (a neurotoxin), TH—Tyrosine Hydroxylase (an enzyme involved in dopamine synthesis), 4-HNE—4-Hydroxynonenal (a marker of oxidative stress), ATC7—Autophagy-related gene 7 (part of the autophagy process), LC2—Light chain 2 (part of the autophagy process), Beclin1—Bcl-2-interacting myosin-like coiled-coil protein 1, SQSTM1—Sequestosome-1 (also known as P62, a protein involved in autophagy), P62—Sequestosome-1, α-Syn—Alpha-synuclein (a protein associated with neurodegenerative disorders), LC3—Microtubule-associated protein 1A/1B-light chain 3 (part of the autophagy process), GDNF—Glial cell-derived neurotrophic Factor, 6-OHDA—6-Hydroxydopamine (a neurotoxin), DA—Dopamine, TNF-α—Tumor necrosis factor-alpha, IL-1β—Interleukin-1 beta, IRS-1—Insulin receptor substrate 1, IRS-1(phospho-S312)—Phosphorylated form of IRS-1 at serine 312, GAPDH—Glyceraldehyde-3-phosphate dehydrogenase (a common housekeeping gene used as a loading control in experiments), DA5-CH—Dopamine-5,6-chlorohydroxydihydroxyphenylalanine, ATG7—Autophagy-related gene 7, LC3II—Microtubule-associated protein 1A/1B-light chain 3 (processed form), LC3I—Microtubule-associated protein 1A/1B-light chain 3 isoform I, ROS—Reactive oxygen species.