Table 1:
Clinical trials with agents/drugs with antioxidant properties in neurodegenerative diseases.
| Antioxidant therapy | Family | Disease | Mechanism of action | Results | Reference |
|---|---|---|---|---|---|
| Resveratrol | Polifenol | AD | It reduces MDA and nitrite production, restores GSH levels and reduces SOD activity. | Studies in vivo e in vitro demonstrate that resveratol may be useful for the treatment of AD not only for its antioxidant effects, but also for its neuroprotective and antiinflammatory effects. | Islam et al. [34] |
| Lipoic acid | Thiol | AD | It upregulates levels of the enzyme glutathione reductase and reduces MDA by increasing antioxidant activity. | It is a supplement with a significant potential in the treatment of AD, and a candidate with positive effects on mitochondrial dysfunction. | Kaur et al. [36] |
| Acetyl-L-carnitine | Acetylated form of L-carnitine | AD | It attenuates cytotoxicity, protein oxidation and lipid peroxidation significantly. It increases levels of cellular GSH. | It helps patients maintain their initial cognitive performance and attenuates the behavioral and psychological symptoms of dementia during treatment. | Mota et al. [37] |
| Omega-3 acid | Polyunsaturated fatty acid | AD | It reduces lipid peroxidation and increases SOD, catalase and GPx activity. | It exerts beneficial effect in the onset of disease in the presence of mild brain function impairment. | Canhada et al. [33] |
| Rasagilina, selegilina | IMAO-B | AD | It increases antioxidant and airon chelator activity. | It prevents tau protein hyperphosphorylation and oxidative stress. It regulates Aβ deposits. It may improve memory and learning capacities. | Behl et al. [35] |
| N-acetylcysteine | Thiol | PD | It reduces lipid peroxidation and SOD activity. It increases GPx and GSH activity. | It seems to induce significant changes in GSH concentrations in CSF, albeit without an immediate improvement of symptoms. | Niedzielska et al. [6] |
| Zonisamide | Sulfonamide | PD | It inhibits glutamate release. It increases levels of 8-OHdG in urine of PD patients. | It is effective in improving motor symptoms as adjuvant agent of standard therapy. | Niedzielska et al. [6] |
| Deferiprone | Iron chelator | PD | It has capacity to rescue iron-overloaded cells, especially mitochondria (the organelles most affected by cell iron accumulation), and reduce ROS formation and the resulting oxidative stress. | The patients who received deferiprone exhibited a significantly better motor performance at 6 or 12 months. | Devos et al. [38] |
| Safranal | Apocarotenoid | HD | It prevents the elevation of 3-NT and MDA levels. It reduces SOD, catalase and GSH activity. | It exerts beneficial effects on motor activity and oxidative brain damage in an animal model. | Fotoohi et al. [39] |
| Epigallocatechin gallate | Polyphenol | HD | It reduces reactive oxygen species and chelation of bonding metal ions. | It helps reduce mHTT accumulation. | Sebastiani et al. [40] |
| Riluzol | Benzothiazole | ALS | It inhibits excessive glutamate production by reducing levels of cytosolic calcium. | It exerts slight beneficial effects by delaying disease progression and increasing survival. | Orrell et al. [41] |
| It induces glutathione synthesis thereby reducing ROS. | Jaiswal et al. [30] | ||||
| Edaravone | Pirazoline | ALS | It eliminates lipid peroxides and hydroxyl radicals. It reduces levels of 3-NT. | It delays progression of functional motor disorders by reducing oxidative stress in ALS patients. | Yoshino et al. [42] |
| Jaiswal et al. [30] | |||||
| Curcumin | Phenolic compound (diferuloylmethane) | ALS | It attenuates oxidative damage and mitochondrial dysfunction. | It slightly slows down disease progression by modulating mitochondrial functions, thereby improving redox state and improving oxidative damage. | Chico et al. [43] |
| Vitamin E | Tocopherol | PD | It attenuates the effects of ROS and inhibits lipid peroxidation. | It was not found to delay functional decline or improve the clinical symptoms of PD. | Shoulson et al. [44] |
| Coenzyme Q10 and derivatives (mitokine mesylate) | Ubiquinone | AD | It reduces levels of MDA and lipid peroxidation. It increases SOD and mitochondrial complex I activity. It reduces oxidative damage. | It improves cognitive decline, oxidative stress, synaptic loss and reduces Aβ accumulation in transgenic animal models of AD. | McManus et al. [32] |
| PD | It plays a limited role in the treatment of PD, since it does not delay functional decline or improve symptoms in PD patients. | Zhu et al. [45] | |||
| HD | The trial does not provide evidence that coenzyme Q10 delays functional decline in HD, and the results do not provide a rationale for this compound to be recommended as a treatment for HD. | McGarry et al. [46] |
3-NT, 3-nitrotyrosine; 8-OHdG, 8-hydroxydeoxyguanosine; Aβ, beta-amyloid protein; AD, Alzheimer’s disease; HD, Huntington’s disease; ALS, amyotrophic lateral sclerosis; PD, Parkinson’s disease; GPx, glutathione peroxidase; GSH, reduced glutathione; B-MAOI, monoamine oxidase B inhibitors; CSF, cerebrospinal fluid; MDA, malondialdehyde; mHTT, mutated HTT protein; ROS, reactive oxygen species; SOD, superoxide dismutase.