TABLE 1.

Antioxidant compounds used in the treatment of ALS.

Antioxidant	Features	Molecular mechanisms	Curative effects and treatment object	References
Vitamin E	- Lipophilic antioxidant - Ability to cross cell   membrane	- Protection against   lipoperoxidation - Protection against ROS   and RNS	- Delay in the clinical onset of   the disease - Increase GSH levels in   plasma - Lower risk of dying by ALS - Significant decrease in the   risk of the disease - Lower ALS rates	Gurney et al., 1996; Desnuelle et al., 2001; Ascherio et al., 2005; Veldink et al., 2007; Wang H. et al., 2011
Carotenes	- Natural pigments - Different types:   ß-carotene, lutein,   astaxanthin and   lycopene	Antioxidant and neutralizing properties against ROS	- Help prevention and/or delay   the onset of ALS - Reduced risk of ALS - Treating neuroinflammation   and apoptosis	Fitzgerald et al., 2013; Krishnaraj et al., 2016
Flavonoids	- Natural substances of   fruits and vegetables - Different types: 7,8-DHF,   fisetin and quercetein	- Protection against ROS - Modulate metabolic   pathways	- Improve motor deficits and   enhance lower neuronal   survival - Reduction of intracellular   ROS levels - Reduction of motor neuron   loss - Improve motor activity and   survival rate - Inhibition of aggregation and   misfolding of SOD1	Korkmaz et al., 2014; Ip et al., 2017; Wang et al., 2018
Resveratrol	- Natural polyphenolic   compound - In grapes, peanuts and   berries - Produced in plants in   response to mechanical   injury, fungal infection,   and UV radiation - Scavenger of free   radicals	- Interacts with mutant   SOD1 (G93A) protein - Up-regulates SIRT1 - Down-regulation of   AMPK/SIRT1 signaling in   bone marrow mesenchymal   stem cells	- Delays the onset of ALS - Increases survival of spinal   motor neurons - Preserves the function of the   lower and upper motor neuron - Attenuates the loss of motor   neurons - Improves muscle atrophy - Improves mitochondrial   function of muscle fibers	Mancuso et al., 2014a, b; Song et al., 2014
Epigallocatechin gallate	- Catechin present in   green tea - Crosses the blood-brain   barrier	- Modulates mitochondrial   responses to OS - Protection against   lipoperoxidation - Changes intracellular   signals - Reduces the   concentration of NF-kB   caspase-3 and iNOS	- Prevents OS-induced death - Delays the outbreak or   progression of ALS - Delays the onset of the   disease - Prolongs useful life - Increases the number of   motor neurons - Decreases the activation of   microglia	Koh et al., 2004, 2006; Xu et al., 2006
Curcumin	- Natural and liposoluble   dye - Obtained from turmeric - Chemical instability - Low oral bioavailability - Low water solubility rate - Different types: DMC	- Activates Nrf2 - Decreases intracelullar   ROS levels - Eliminates excitability   induced by TDP-43 - DMC decreases   mitochondrial dysfunction	- Improves survival - Decrease in ALS progression   and reduction of oxidative   damage	Ahmadi et al., 2018; Chico et al., 2018
Co-enzyme Q10	- Endogenous antioxidant	- Cofactor of the ETC - Action in redox balance - Improves mitochondrial   dysfunction	- Increases survival rate	Matthews et al., 1998; Beal, 2002
Melatonin	- Amphiphilic molecule - Potent antioxidant	- Antioxidant - Regulator of mitochondrial   bioenergetic function	- Delays the progression of the   disease - Increases the survival rate	Zhang et al., 2013 Weishaupt et al., 2006
Edaravone	- Low-molecular-weight   antioxidant drug - Intravenously   administered - Free radical scavenger - Safe - Crosses the blood-brain   barrier easily - High brain penetration   capacity - Amphiphilic capacity - Scavenges lipid and   water soluble peroxyl   radicals and chain-  carrying lipid peroxyl   radicals	- Enhances prostacycling   production - Traps hydroxyl radical and   quenches active oxygen	- Deletes lipid peroxides and   hydroxyl radicals during   cerebral ischemia - Protects nerve cells within or   around the ischemic region   from free radical damage - Ameliorates OS and   suppresses degeneration of   spinal motor neurons - Anti-inflammatory and   protective effects on neurons,   microglia, astrocytes and   oligodendrocytes - Delays the progression of   functional motor disturbances	Ikeda and Iwasaki, 2015; Banno et al., 2005; Yoshino and Kimura, 2006; Miyamoto et al., 2013; Abe et al., 2014; Bailly, 2019