Quinones as Neuroprotective Agents

Abstract

Quinones can in principle be viewed as a double-edged sword in the treatment of neurodegenerative diseases, since they are often cytoprotective but can also be cytotoxic due to covalent and redox modification of biomolecules. Nevertheless, low doses of moderately electrophilic quinones are generally cytoprotective, mainly due to their ability to activate the Keap1/Nrf2 pathway and thus induce the expression of detoxifying enzymes. Some natural quinones have relevant roles in important physiological processes. One of them is coenzyme Q10, which takes part in the oxidative phosphorylation processes involved in cell energy production, as a proton and electron carrier in the mitochondrial respiratory chain, and shows neuroprotective effects relevant to Alzheimer’s and Parkinson’s diseases. Additional neuroprotective quinones that can be regarded as coenzyme Q10 analogues are idobenone, mitoquinone and plastoquinone. Other endogenous quinones with neuroprotective activities include tocopherol-derived quinones, most notably vatiquinone, and vitamin K. A final group of non-endogenous quinones with neuroprotective activity is discussed, comprising embelin, APX-3330, cannabinoid-derived quinones, asterriquinones and other indolylquinones, pyrroloquinolinequinone and its analogues, geldanamycin and its analogues, rifampicin quinone, memoquin and a number of hybrid structures combining quinones with amino acids, cholinesterase inhibitors and non-steroidal anti-inflammatory drugs.

Insight into the Antioxidant Activity of 1,8-Dihydroxynaphthalene Allomelanin Nanoparticles

“…These findings suggest that PDHN-NP may be useful to protect substrates whose autoxidation is also mediated by HOO • radicals, such as amines, alcohols, and 1,2 or 1,4 cyclohexadiene derivatives [ 48 ]. As HOO • and its conjugated base superoxide (O 2 •− ) are commonly present in biological systems as a result of O 2 •− leakage from the respiratory chain and as an effect of NADPH oxidase (NOX) activity [ 48 ], it can be envisaged that PDHN-NP may be capable of capturing reducing equivalents from superoxide and of using them to stop the peroxidation of important biomolecules in a catalytic fashion [ 73 ]. This antioxidant activity may act in synergy with the known protective effect against UV light.…”

“…•− leakage from the respiratory chain and as an effect of NADPH oxidase (NOX) activity [48], it can be envisaged that PDHN-NP may be capable of capturing reducing equivalents from superoxide and of using them to stop the peroxidation of important biomolecules in a catalytic fashion [73]. This antioxidant activity may act in synergy with the known protective effect against UV light.…”

Lipid Peroxidation in Muscle Foods: Impact on Quality, Safety and Human Health

“…Synergistic effects are enhanced when the two inhibitors are used to act as peroxide scavengers or chelators, facilitating the interaction between free radicals and thus terminating the chain reaction [ 20 , 254 , 317 ]. Synergists can also include compounds that lack antioxidant properties or exhibit very weak antioxidant activity [ 318 , 319 , 320 ]. Certain amino acids, polyphosphates, cephalic, sulfhydryl, and other compounds act as active synergists in inhibiting lipid peroxidation in meat and fish products [ 321 , 322 , 323 , 324 ].…”

Oxidative Stress and the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Pathway in Multiple Sclerosis: Focus on Certain Exogenous and Endogenous Nrf2 Activators and Therapeutic Plasma Exchange Modulation

“…There, Nrf2 heterodimerizes with small musculoaponeurotic fibrosarcoma (sMaf) proteins and binds to antioxidant response elements (ARE) in the promoter region of target genes [48][49][50][51][52]. This region encodes several antioxidant enzymes that neutralize ROS and electrophiles, involving superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, glutathione reductase, and heme oxygenase-1 (HO-1) (Figure 2) [53,54].…”