Table 2.

Mitochondria targeted agents (small molecules) in other than ALS indications.

S. No.	Interventions	Structure	Mechanism	Disease Condition	References
1	All-trans retinoic acid (ARTA/Retinoic acid)		Retinoic acid used for Mitochondria biogenesis and stimulated the retinoid X receptor-α (RXRα) to repair the mitochondrial respiratory chain defect	Lipid metabolism	[119, 148]
2	KH176		Intracellular reduction-oxidation-modulating compound used for the management of mitochondrial diseases	MELAS, LHON, Leigh, and other MDs	NCT02544217 & [149]
3	Bezafibrate		Mitochondrial biogenesis and PPAR-α activation	Mitochondrial myopathy	[150]
4	L-Arginine		Improvement in aerobic capacity and muscle metabolism	Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like syndrome (MELAS)	NCT01603446 & [151]
5	Rapamycin		Improves motor endurance, muscle morphology, activation of autophagy via mTOR-dependent pathways and mitochondrial structure	Mitochondrial myopathy	[119, 152]
6	Vatiquinone or EPI-743		EPI-743 works by enhancing the regulation of cellular energy metabolism by directing NADPH quinone oxidoreductase 1 (NQO1)	Leigh Syndrome and congenital respiratory chain diseases	[153]
7	Idebenone		Idebenone stimulated the mitochondrial permeability transition pore (mPTP)	Leber Hereditary Optic Neuropathy (LHON)	[154]
8	Cysteamine bitartrate		Antioxidant properties by enhancing glutathione biosynthesis	Mitochondrial respiratory chain disease	[155]
9	Omaveloxolone		Omaveloxolone is an Nrf2-inducer, reduces Inflammation, provides protective shelter to mitochondrial depolarization, promoting mitochondrial respiration and preventing cell death	Friedreich’s Ataxia (FRDA): an autosomal recessive neurodegenerative disorder	[156]
10	Taurine		Neuroprotector by decreasing ER stress and antagonizing neurotransmitter receptors of GABAA, glycine and NMDA	Myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)	[157, 158]
11	L-Carnitine		L-carnitine translocate the fatty acids into the mitochondrial compartment for β-oxidation. Role in carbohydrate metabolism like ketogenesis and glucogenesis. Elimination of toxic metabolites	Mitochondrial dysfunction, Chronic progressive external ophthalmoplegia (CPEO)	[159, 160]
12	Tetracycline		Antiapoptotic, antiinflammation, antioxidation and improves fitness	Mitochondrial dysfunction and Leigh syndrome	[160, 161]
13	Doxycycline		Prevents neuronal death and the accumulation of neuroimmune and inflammatory proteins	Mitochondrial dysfunction	[161]
14	Pioglitazone		Peroxisome proliferator-activated receptor gamma (PPARγ) agonist	Pioglitazone improves lipopolysaccharide-induced behavioural loss, inflammation, white matter injury and mitochondrial dysfunction, inhibits diabetes-induced atrial mitochondrial oxidative stress and improves mitochondrial biogenesis, dynamics	[162, 163]
15	Sonlicromanol		Improves neuronal network dysfunction	Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)	[164]
16	Oleanolic acid		Rescued mitochondrial ultra-structure anomalies and mitochondrial biogenesis	Cardiac aging	[165]