Focusing on mitochondria in the brain: from biology to therapeutics

Table 2 Mitochondrial therapeutics for brain diseases

Drugs/Chemicals	Mechanisms	Pathological conditions	References
Mitochondria-targeting agents
MSDC-0160	Reduce the activity of mitochondrial pyruvate carrier	AD, PD	[381, 382]
NMN and NR	NAD⁺ supplement	Ageing, NDDs,	[384,385,386,387]
SBT-272	Restore mitochondrial structure and respiratory function	ALS	[388]
SS-31	Mitochondria-targeting antioxidant	AD, HD	[389, 391]
MitoQ	Mitochondria-targeting antioxidant	HD, aging-associated memory loss	[390, 391]
Trehalose	Autophagy inducer	NDDs, MNDs, MS	[203, 396,397,398,399,400]
Latrepirdine	Autophagy inducer	AD, PD	[204, 403,404,405]
Spermidine	Autophagy inducer	Ageing, neurodegeneration	[206, 250, 401, 402]
ATC161	Degradation of α-syn aggregates by p62-dependent autophagy	NDDs	[406, 407]
UMI-77	Mitophagy activator	AD	[408]
Mdivi-1	Mitochondrial fission inhibitor	NDDs, ischemic stroke	[409,410,411]
P110	Mitochondrial fission inhibitor	NDDs	[128]
Coniferaldehyde	Nrf2 activator that protects mitochondria by promoting mitochondrial biogenesis	AD	[420]
SBT-272	Restoring mitochondrial structure and respiratory function	ALS	[388]

Drugs	Mechanisms	Approved application	Repurposed application	References
Repurposing mitochondria-targeted FDA-approved drugs in brain disease therapy
Edaravone	Mitochondria-targeting antioxidant	ALS	Ischemic stroke	[425]
Atovaquone	Inhibit mitochondrial electron transport	PCP; Plasmodium falciparum malaria	Toxoplasmic encephalitis	[426, 427]
Bedaquiline	Inhibit mitochondrial ATP synthase	MDR-TB	Ischemic stroke	[428]
Idebenone	Mitochondria-targeting antioxidant	LHON	AD, PD, HD	[421, 429, 430]
Pioglitazone	Agonism of PPARγ	Type 2 diabetes mellitus	AD, dementia, PD and ischemic stroke	[412,413,414,415]
Bezafibrate	Pan-PPAR activator	Hyperlipidaemia	NDDs	[418, 419]
Metformin	Induce autophagy by activation of the AMPK-mTOR signaling	Type 2 diabetes mellitus	Ageing, NDDs	[392,393,394,395]

AD: Alzheimer’s disease; ALS: Amyotrophic lateral sclerosis; LHON: Leber’s Hereditary Optic Neuropathy; Mdivi-1: mitochondrial division inhibitor 1; MDR-TB: Pulmonary multidrug resistant tuberculosis; MND: Motor neuron disease; MS: multiple sclerosis; NAD⁺ : nicotinamide adenine dinucleotide; NDD: neurodegenerative disease; NMN: nicotinamide mononucleotide; NR: nicotinamide riboside; PCP: Pneumocystis jirovecii pneumonia; PD: Parkinson's disease; PPARγ: peroxisome proliferator-activated receptor-gamma

ISSN: 2047-9158