Table 1.

A summary of the quinones described in this review.

Quinone	Properties	Refs.
Coenzyme Q10	ROS scavenger in the mitochondria, Nrf2 inductor [38,39]. Anti-inflammatory effects, decreasing the protein and mRNA levels of pro-inflammatory cytokines. Anti-apoptotic properties [40]. Increases the levels of tyrosine hydroxylase [45].	[38,39,40,45]
QS-10	Activation of the Keap1/Nrf2 pathway. Activation of the heat-shock transcription factor-1 (HSF-1).	[51]
Idebenone	Treatment for complex I-related diseases: Leber’s hereditary optic neuropathy (LHON) Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), Duchene muscular dystrophy and glaucoma. Under clinical assay for Friedreich ataxia (FRDA) [55], multiple sclerosis [56] and Parkinson’s disease [57].	[53,54,55,56,57]
Mitoquinone	Treatment of Parkinson’s disease [58] and multiple sclerosis [59].	[58,59]
SkQ1	Neuroprotective properties in a model of middle cerebral artery occlusion, when introduced immediately after reperfusion [61]. Neuroprotective properties in models of Alzheimer’s disease [62].	[61,62]
Vatiquinone (EPI-743, α-tocotrienol quinone)	Modulates the oxidative stress response [67]. Prevents ferroptotic cell death in some neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases [68,70] Treatment of Leigh syndrome and other inherited mitochondrial diseases [71]. FDA orphan drug status for the treatment of Friedrich’s ataxia [72].	[67,68,69,70,71,72]
MK-4	Prevents the depletion of glutathione mediated by free radical-mediated oxidative injury [81].	[81]
Menadione (vitamin K3)	Protects neurons from methylmercury-induced cell death [75]. Inhibits the aggregation of the Aβ1–42 protein, and it is also neuroprotective against Aβ1–42 insult in human neuroblastoma cells (SH-SY5Y) [82]. Competitive inhibitor of monoamino oxidases (MAO), with some selectivity for MAO-B [83].	[75,82,83]
Embelin	Inhibits beta-secretase 1 (BACE-1), acetylcholinesterase and butyryl cholinesterase, with a balanced multitarget profile [88]. Reduces cognitive deficit in a scopolamine-induced Alzheimer’s disease-like condition in a rat model [90]. Potent radical scavenger [91]. Anti-inflammatory properties [92].	[88,90,91,92]
SB-1448	Inhibits acetylcholinesterase and butyryl cholinesterase [93]. Inhibits Aβ self-aggregation [93]. Reduces scopolamine-induced cognitive impairments in mouse models [93].	[93]
APX-3330 (E-3330)	Treatment of diabetic retinopathy by APE1/Ref-1 inhibition [98].	[98]
APX-2009 APX-2014	Targets neovascular eye diseases by APE1/Ref-1 inhibition [98].	[98]
VCE-003	Alleviates neuroinflammation in a chronic model of multiple sclerosis by PPARγ activation [99].	[99]
VCE-003.2	Enhances neuronal progenitor cell survival and to also provide a symptomatic relief in murine models of Huntington’s disease [101]. Showed protective effects in SOD1G93A transgenic mice, a model of amyotrophic lateral sclerosis [102].	[101,102]
HU-331	Anticancer properties [103]. Activation of the Keap1-Nrf2 pathway and BACH1 inhibitors [104].	[103,104]
Quinones 1	Neuroprotective activity [105].	[105]
Asterriquinone B4	Neuroprotective activity in several cellular using oxidative stress models of Parkinson’s disease [106].	[106]
Asterriquinone 1H5 Indolylquinone 5E5	Promote neuronal differentiation of PC12 cells [107].	[107]
PQQ	Potent radical scavenger [113]. Reduces oxidative stress by increasing the expression of Nrf2 [115]. Neuroprotection of primary cultured hippocampal neurons against glutamate-induced cell damage by activation of the PI3K/Akt pathway [116]. Reduced indirectly the activity of GSK-3β [117]. Exerted effective protection in SH-SY5Y cells against 6-hydroxydopamine-induced neurotoxicity [113,114]. Reduce oxidative stress and improve mitochondrial functions and dopamine redistribution [118].	[113,114,115,116,117,118]
Geldanamycin	Binds to Hsp90 a target in neurodegeneration [119,120,121]. Protects against MPTP-induced dopaminergic neurotoxicity [123]. Rescues striatal dopamine levels [124]. Suppresses memory deficits in β-amyloid-injected rats [125]. Induces the degradation of misfolded tau protein [126]. Reduces brain injury in a mouse model of intracerebral hemorrhage and improves the neurological outcome of these mice [127].	[119,120,121,123,124,125,126,127]
Tanespimycin	Reduces polyglutamine-mediated motor neuron degeneration through proteasomal degradation of the androgen receptor in a mouse model [129]. Improves balance and coordination in a mouse model of the Machado-Joseph disease (spinocerebellar ataxia type 3) [130].	[129,130]
Rifampicin quinone	Inhibits fibrillation and disaggregates formed fibrils of β-amyloid [134]. Ameliorates the neurotoxic effects mediated by α-synuclein in microglial cells [136]. Protects PC12 cells against apoptosis induced by N-methyl-4-phenylpyridinium (MPP+). Suppresses the expression of α-synuclein multimers [139].	[134,136,139]
Thymoquinone	Protects against ischemic brain damage and reduces oxidative damage associated to epileptic seizures [142].	[142]
Juglone	Inhibits BACE and Aβ aggregation and induce Aβ fibril disaggregation [143]. Reverses the Thr-231 dephosphorylation of Tau induced by oxidative or heat stress in primary cortical cultures [145]. Neuroprotective potential by redox cycling [146] acting as a chelating agent [147]	[143,145,146,147]
Plumbagin	Reduces the extent of brain damage and neurological deficit associated to middle cerebral artery occlusion/reperfusion in mice [148]. Activates the Nrf2-ARE pathway, inhibits BACE-1 and attenuates astrocyte hyperactivation [149]. Inhibits the NF-kB pathway [150] and displays antioxidant and chelating activities [151].	[148,149,150,151]
Naphthoquinone 4	Inhibits the aggregation of Aβ40 and the PHF6 tau fragment [152]. Inhibits AChE and MAO B [152].	[152]
Purpurin	Hampers the aggregation of PHF-6 and diassambles pre-formed PHF-6 fibrils, reducing Tau phosphorylation and accumulation [153]. Inhibits NF-κB activation [154]. Decreases oxidative stress and inflammation markers [155].	[153,154,155]
Emodin	Radical scavenger and chelating agent. Nrf2 inducer. Inhibits Aβ42 and Tau aggregation and toxicity. Inhibits AChE and BACE [152].	[152]
Rhein	Treatment of traumatic brain injury (TBI) by attenuating inflammation markers, pyroptosis and neurological dysfunction [158,160]. NADPH oxidase inhibition, avoiding the increase of ROS levels [159]. Modulation of inflammatory response by NF-kB-pathway and NLRP-3 inflammasome inhibition [161]. Moderate inhibition of AChE [183].	[158,159,160,161,183]
Compounds 5	Neuroprotective activity against H2O2-induced oxidative stress. Reduces the levels of inflammatory cytokines and NO produced by macrophages exposed to LPS. Inhibits the production and aggregation of Aβ. Moderate AChE and BChE inhibition [164].	[164]
Quinones 6	Inhibits the JAK-STAT pathway [165].	[165]
Memoquin	Scavenges ROS. Inhibitis β-amyloid aggregation, BACE-1 and AChE [174]. Prevents cognitive impairment [173].	[173,174]
Compound 7	Inhibits BACE [175].	[175]
Compounds 8	Inhibit ROS production and ROS-induced cytotoxicity. Induce Nrf2, thereby increasing the levels of the NQO1 enzyme [176]. Reduce Aβ42 self-aggregation. Inhibit AChE and BChE [177].	[176,177]
Compounds 9	Inhibit β-amyloid aggregation Inhibit AChE [178].	[178]
Compounds 10	Inhibit AChE. Inhibit spontaneous amyloid aggregation [179].	[179]
Compounds 11	Inhibit AChE. Radical scavengers [180].	[180]
Compounds 12	Selectively inhibit butyrylcholinesterase. Antioxidant and amyloid antiaggregating properties [181].	[181]
Compounds 13	Inhibit both AChE and BChE. Inhibit β-amyloid aggregation [182].	[182]
Compounds 14	Inhibit AChE [183].	[183]
Compounds 15	Inhibit AChE and BChE. Inhibit BACE-1. Show dual Aβ42 and tau antiaggregating activity [185].	[185]
NQTrp	Reduces the accumulation of oligomeric Aβ species in an Alzheimer’s disease model of Drosophila flies [188]. Inhibits the aggregation of α-synuclein.	[188]
NQDA	Inhibits α-synuclein aggregation and disrupts preformed fibrils. Reduces aggregate-induced toxicity [189]	[189]