Table 2.
MTAs in PD models and clinical trials.
| Mitochondria-targeted antioxidants | Models/clinical trials | Dosage | Effects/mechanism | Reference |
|---|---|---|---|---|
| MitoQ | Cellular MPP+ model | 50 nmol/L in culture medium | (1) Inhibited MPP+-induced decrease in dopamine levels | [93] |
| Mouse MPTP model | 4 mg/kg∗bodyweight; oral gavage | (1) Protected the nigrostriatal axis against MPTP toxicity (2) Improved locomotor activities in MPTP-treated mice (3) Inhibited mitochondrial aconitase inactivation |
[93, 96] | |
| Cellular 6-OHDA model | 10-200 nmol/L in culture medium | (1) Blocked 6-OHDA-induced mitochondrial fragmentation | [97] | |
| Mouse 6-OHDA model | 5 mg/kg∗bodyweight; intragastric administration | (1) Rescued dopamine neurons loss in SNc (2) Protected dopamine neurons via activating PGC-1α and enhance Mfn2-dependent mitochondrial fusion |
[97] | |
| Clinical trial | Daily 40/80 mg; oral administration | (1) Slowed the progression of Parkinson's disease as measured by the UPDRS (2) No difference in the measured parameters between the treatment and the placebo |
NCT00329056 | |
|
| ||||
| SS-20/Phe-D-Arg-Phe-Lys-NH2 | Cellular MPP+ model | 1-10 nmol/L in culture medium | (1) Rescued mitochondrial oxygen consumption and ATP production damaged by MPP+ (2) SS-20 (4 mg/kg∗bodyweight) protected against the loss of dopaminergic neurons in the substantia nigra pars compacta |
[94] |
| Mouse MPTP model | 0.5-5 mg/kg∗bodyweight; intraperitoneal injection | |||
|
| ||||
| SS-31/D-Arg-(2′6′-dimethyltyrosine)-Lys-Phe-NH2 | Cellular MPP+ model | 1-10 nmol/L in culture medium | (1) Improved cell survival and motor performance (2) Decreased cell loss and oxidative stress in the lumbar spinal cord (3) SS-31 (10 mg/kg∗bodyweight) protected against the loss of dopamine and its metabolites |
[94] |
| Mouse MPTP model | 0.5-10 mg/kg∗bodyweight; intraperitoneal injection | |||
|
| ||||
| P68+DQA nanocarriers NAC |
Cellular rotenone PD model | 1000 μmol/L in culture medium | (1) P68+DQA nanocarrier delivery system enhanced the stability, bioavailability, and brain penetrance of NAC (2) Formulation of NAC into P68+DQA nanocarriers rescued cell viability and alleviated oxidative stress |
[95] |
Notes: 6-OHDA: 6-hydroxydopamine; DQA: dequalinium; Mfn2: mitochondrial GTPase mitofusin-2; MPP+: 1-methyl-4-phenylpyridinium; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NAC: N-acetylcysteine; P68: Pluronic F68; PD: Parkinson's disease; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1 alpha; SNc: substantia nigra pars compacta; UPDRS: Unified Parkinson's Disease Rating Scale.