Table 2.

Phytochemicals and other chemicals used for mitochondrial-targeted therapies in AD models in preclinical and clinical studies.

Phytochemical/Drug Candidate	AD Model	Mitochondrial Effect	References
Melatonin	HEK293-APPswe AD model	Increase of mitochondrial biogenesis and mitochondrial membrane potential, Decrease of APP processing	[118]
Coenzyme Q10	TgP301S mice, M17 cell line treated with Aβ1-42 peptide, HUVEC cell line Aβ25-35 peptide-treated	Decrease of ROS levels, Reduction of the accumulation of Aβ peptide, mtΔΨ protection, Promotion of ETC	[119,120]
Astaxanthin	Mouse hippocampal neurons treated by Aβ1-42 oligomers	Reduction of mitochondrial Production of H2O2	[121]
Resveratrol	APP/PSEN1 mice	Activation of mitophagy, Reduction of ROS accumulation	[122]
Pioglitazone	APP/PSEN1 mice	Reduction of Aβ1-42 level, Restoration of mitochondrial function	[123]
Dimebon	Mild-to-moderate AD patients	Improvement of cognition and memory function	[124]
Oxaloacetate (OAA)	AD cultured cells and mice	Activation of mitochondrial biogenesis	[125]
2-deoxyglucose	Adult rats treated with Aβ peptides	Increase in mitochondrial biogenesis, Reduction of mitochondrial stress	[126]
Curcumin	APP/PSEN1 mice, APP751SL mice	ROS reduction, Increase in synaptic function	[109]
Epigallocatechin-3-gallate (EGCG)	APP/PSEN1 mice	Restoration of mitochondria respiratory rates, Reduction of ROS and Aβ	[127]
Catalase	MCAT/APP mice	Reduction of oxidative damage, Aβ, BACE1 activity, and APP processing	[128]
α-lipoic acid	AD patients	Increase in cognition function, Protection against Aβ toxicity	[129]
N-Acetyl-cysteine (NAC)	A double-blind AD patient	Improvement of cognitive and behavioral functions	[130]
Quercetin	APP/PSEN1 mice	Improvement of ΔΨ, Prevent intrinsic apoptosis	[54]
G. biloba	Older adults and AD patients	Prevention of cognition and memory decline	[131]
SkQ1	OXYS rats	ROS reduction, COX increase	[132]
SS31	APP mouse model (Tg2576)	Decrease in Aβ production and dysfunction, Stimulation of mitochondrial biogenesis and	[133]
Ketones	3xTgAD)	Enhancement of mitochondrial functions and dynamics	[134,135]
Rapamycin	Aβ treated PC12 cell line	Increase in mitophagy	[136]
Red ginseng (RG)	5XFAD mice	Amelioration of Aβ deposition, Increase in mitochondrial biogenesis	[137]
Thiosemicarbazones	AD model of SK-N-MC neuroepithelioma cells	Inhibition of Aβ deposit formation, Reduction in ROS levels	[138]