Table 1.

Mitochondria based therapeutic interventions of ALS along with their molecular mechanism and disease conditions.

S. No.	Interventions	Structure	Mechanism	Disease Condition	References
1	Exercise or Aerobic endurance		Mitochondrial biogenesis and increased muscle mitochondrial enzyme activities and muscle strength	ALS: Mitochondrial Diseases like Mitochondrial myopathy in ALS and other indications	[119-123]
2	Riluzole		Diminishes the ROS generation via anti-glutamatergic effects tendency and attenuates inward calcium current	ALS: Maintaining mitochondrial calcium buffering mechanisms in ALS	[112, 113]
3	Edaravone		Neuro-protective effect by boosting prostacyclin production, reducing lipoxygenase metabolism of arachidonic acid by blocking hydroxyl radicals, preventing alloxan-induced lipid peroxidation and quenching active oxygen species	ALS: Free radical scavenger and antioxidant in ALS	[115]
4	Fenofibrate		PPAR-α activation	ALS: Neuroinflammation and mitochondrial dysfunction in ALS	[124]
5	Vitamins C (Ascorbic Acid)		Endogenous defensive strategy against oxygen free radicals in mitochondria Protection against lipoperoxidation	ALS: Electron carrier and Antioxidant in ALS	[125]
6	Vitamin E (α-tocopherol)		Protection against lipoperoxidation	ALS: Lipophilic antioxidant has the ability to cross cell membrane resulting in delay and lower risk of clinical onset in ALS Decrease in plasma levels of thiobarbituric acid reactive species	[126, 127]
7	Co-enzyme Q10 (CoQ10)		A strong lipid oxidants scavenger, which participates in transferring electrons from mitochondrial complexes I and II to mitochondrial complex III. CoQ10: stabilizes mitochondrial membrane potential, prevents cytochrome c release; inhibits mitochondrial permeability transition pore, and blocks. Bax translocation to mitochondria	ALS: Stabilized the motor neuron function in neuro-degenerative disorders like ALS and other indications	[128-131]
8	Glutathione (GSH)		Antioxidant property: Neuronal GSH helps in the protection of neurons in the brain against ROS and oxidative damage	ALS: Regulates the development and progression of Amyotrophic Lateral Sclerosis	[132]
9	Resveratrol		Inhibits mutant SOD1 (G93A) protein, up-regulates SIRT1, down-regulates AMPK/SIRT1 signalling and activates mitochondrial biogenesis	ALS: Improves muscle atrophy and mitochondrial dysfunction in ALS and other indications	[133-135]
10	β-carotene		Antioxidant properties	ALS: Neuroinflammation and apoptosis in ALS.	[136]
11	7,8-Dihydroxy-flavone (7,8-DHF)		Modulates metabolic pathways and Improves motor deficits and enhances lower neuronal survival	ALS: Chronic administration of 7,8-DHF improved motor deficits in ALS	[137]
12	Epigallocatechin Gallate		Protection against Lipoperoxidation, diminishes the level of NF-kB, caspase-3 and iNOS	ALS: Delays the advancement of ALS by alterations in intracellular signals, enhances survival signals (like PI3-K and Akt) and lowers death signals (like GKS-3ß, cytosolic cytochrome c, activated caspase3 and cleaved poly ADP-ribose polymerase) in ALS and other indications	[138-140]
13	Curcumin		Activates Nrf2, reduces intra-cellular ROS levels, and eradicates excitability induced by TDP-43	ALS: Decreases ALS progression by reducing oxidative damage and improves survival, especially in bulbar onset patients	[140, 141]
14	Melatonin		Antioxidant effect regulates mitochondrial dysfunction and bioenergetic function	ALS: Orally high doses delayed ALS progression via caspase-1/cytochrome c/caspase-3 cell death pathway, inhibits MT1 receptor loss and increases the survival rate	[141-143]
15	SBT-272	NA	Novel peptidomimetic, a role in mitochondrial energetics, by increasing ATP production and decreasing levels of reactive oxygen species (ROS) in dysfunctional mitochondria	Amyotrophic lateral sclerosis (ALS)	Stealth BioTherapeutics
16	MitoQ	-	Accumulates within mitochondria and protects it from oxidative damage	ALS: slowed the mitochondrial functional decline in the spinal cord and muscle; decreased nitroxidative damage in the nervous system; increased survival and slowed the progression of ALS symptoms.	[144]
17	Albrioza	-	Reduces neuronal death by blocking key cellular death pathways of mitochondria and endoplasmic reticulum	ALS: neuronal protection	[116-118]