Therapeutic use of coenzyme Q<sub>10</sub>and coenzyme Q<sub>10</sub>-related compounds and formulations

Villalba, José M.; Parrado, Cristina; Santos‐González, Mónica; Alcaı́n, Francisco J.

doi:10.1517/13543781003727495

Cited by 123 publications

(95 citation statements)

References 169 publications

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“…34,56,57 In addition, the favorable safety profile of idebenone and its dual mechanism of action led to the investigation of its use in other neurodegenerative diseases with mitochondrial impairment. 33,34 FIGURE 3. Detection of senescence-associated b-galactosidase activity is shown in A: Treatment of primary human ONHA with 10 mM idebenone did not lead to significantly increased number of cells that were developing the typical color (dark grey) for b-galactosidase activity compared to the untreated control cells.…”

Section: Discussionmentioning

confidence: 99%

“…27 Beneficial effects of idebenone have been demonstrated in the treatment of several neurodegenerative diseases in which glial tissue is involved in the pathogenesis, including the Leber hereditary optic neuropathy. [28][29][30][31][32][33] Besides the antioxidant properties of idebenone, effects of the substance on expression of antiapoptotic proteins also have been described. 34,35 Oxidative stress is a pathological condition in which the rate of reactive oxygen species (ROS) production exceeds the body's antioxidative capacity.…”

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confidence: 99%

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Idebenone Prevents Human Optic Nerve Head Astrocytes From Oxidative Stress, Apoptosis, and Senescence by Stabilizing BAX/Bcl-2 Ratio

Kernt

Arend

Buerger

et al. 2013

Journal of Glaucoma

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Purpose: Oxidative stress plays an important role in the pathogenesis of several neurodegenerative diseases including glaucoma. Astrocytes are supposed to play a role in glaucoma pathogenesis. This study investigates the antiapoptotic and cytoprotective effects of idebenone on optic nerve head astrocytes (ONHA) under oxidative stress.Methods: ONHA were treated with 1 to 150 mM idebenone. Cell viability (MTT assay and live-dead assay), induction of intracellular reactive oxygen species, senescence-associated b-galactosidase activity were investigated. In addition, apoptosis (detection of histone-associated DNA fragmentation), and expression of BAX and Bcl-2, and their mRNA were determined after 48 hours and after hydrogen peroxide (H 2 O 2 ) treatment.Results: Idebenone concentrations from 1 to 50 mM showed no effects on ONHA viability. Pretreatment with 10 mM idebenone led to an increase in viability of ONHA after H 2 O 2 treatment. In addition, idebenone pretreatment significantly attenuated the increase of histone-associated DNA fragmentation, induction of senescence-associated b-galactosidase, and intracellular reactive oxygen species after treatment with H 2 O 2 . When ONHA cells were treated with idebenone and H 2 O 2 , real-time polymerase chain reaction and Western blot analysis yielded an increased expression of Bcl-2 and a decrease of BAX compared with those cells that were treated with H 2 O 2 only.Conclusions: Idebenone reduced senescence, oxidative stress, and apoptotic cell death in cultured ONHA in vitro. Our results suggest that idebenone may help to protect ONHA in vivo, and therefore might be helpful in preventing the progression of glaucomatous degeneration.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Idebenone Prevents Human Optic Nerve Head Astrocytes From Oxidative Stress, Apoptosis, and Senescence by Stabilizing BAX/Bcl-2 Ratio

Kernt

Arend

Buerger

et al. 2013

Journal of Glaucoma

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“…Furthermore, data collected from human and rodent cellular models show that CoQ 10 affects gene expression and inhibits the release of IL-6 and TNF-α, consistent with its anti-inflammatory effects (Schmelzer et al, 2007(Schmelzer et al, , 2008. Far less convincing benefits are reported for neurodegenerative diseases, such as PD (Shults and Haas, 2005;Shults et al, 2002;Villalba et al, 2010). However, CoQ 10 supplementation of pediatric patients with Down syndrome has produced promising results, pointing out to a potential role of CoQ 10 in a modulation of DNA repair mechanisms Tiano et al, 2012).…”

Section: Introductionmentioning

confidence: 94%

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Sikorska

Lanthier

Miller

et al. 2014

Neurobiology of Aging

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Although the support for the use of antioxidants, such as coenzyme Q 10 (CoQ 10 ), to treat Parkinson's disease (PD) comes from the extensive scientific evidence, the results of conducted thus far clinical trials are inconclusive. It is assumed that the efficacy of CoQ 10 is hindered by insolubility, poor bioavailability, and lack of brain penetration. We have developed a nanomicellar formulation of CoQ 10 (Ubisol-Q 10 ) with improved properties, including the brain penetration, and tested its effectiveness in mouse MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) model with the objectives to assess its potential use as an adjuvant therapy for PD. We used a subchronic MPTP model (5-daily MPTP injections), characterized by 50% loss of dopamine neurons over a period of 28 days. Ubisol-Q 10 was delivered in drinking water. Prophylactic application of Ubisol-Q 10 , started 2 weeks before the MPTP exposure, significantly offset the neurotoxicity (approximately 50% neurons died in MPTP group vs. 17% in MPTP+ Ubisol-Q 10 group by day 28). Therapeutic application of Ubisol-Q 10 , given after the last MPTP injection, was equally effective. At the time of intervention on day 5 nearly 25% of dopamine neurons were already lost, but the treatment saved the remaining 25% of cells, which otherwise would have died by day 28. This was confirmed by cell counts, analyses of striatal dopamine levels, and improved animals' motor skill on a beam walk test. Similar levels of neuroprotection were obtained with 3 different Ubisol-Q 10 concentrations tested, that is, 30 mg, 6 mg, or 3 mg CoQ 10 /kg body weight/day, showing clearly that high doses of CoQ 10 were not required to deliver these effects. Furthermore, the Ubisol-Q 10 treatments brought about a robust astrocytic activation in the brain parenchyma, indicating that astroglia played an active role in this neuroprotection. Thus, we have shown for the first time that Ubisol-Q 10 was capable of halting the neurodegeneration already in progress;

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“…5−8 CoQ10, also known as ubiquinone, is a naturally occurring lipid-soluble, vitamin-like substance that is found in the inner mitochondrial and cellular membranes and in blood; both in high-and in low-density lipoproteins. 9 CoQ10 is a benzoquinone derivative with 10 monounsaturated transisoprenoid units in the side chain ( Figure 1). 10 It functions primarily as a cofactor for the mitochondrial enzymes (complexes I−III) for the oxidative phosphorylation production of adenosine triphosphate (ATP) and is involved in several aspects of cellular metabolism.…”

Section: ■ Introductionmentioning

confidence: 99%

Design and Evaluation of Multifunctional Nanocarriers for Selective Delivery of Coenzyme Q10 to Mitochondria

et al. 2011

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Impairments of mitochondrial functions have been associated with failure of cellular functions in different tissues, leading to various pathologies. We report here a mitochondria-targeted nanodelivery system for coenzyme Q10 (CoQ10) that can reach mitochondria and deliver CoQ10 in adequate quantities. Multifunctional nanocarriers based on ABC miktoarm polymers (A = poly(ethylene glycol (PEG), B = polycaprolactone (PCL), and C = triphenylphosphonium bromide (TPPBr)) were synthesized using a combination of click chemistry with ring-opening polymerization, self-assembled into nanosized micelles, and were employed for CoQ10 loading. Drug loading capacity (60 wt %), micelle size (25−60 nm), and stability were determined using a variety of techniques. The micelles had a small critical association concentration and were colloidally stable in solution for more than 3 months. The extraordinarily high CoQ10 loading capacity in the micelles is attributed to good compatibility between CoQ10 and PCL, as indicated by the low Flory−Huggins interaction parameter. Confocal microscopy studies of the fluorescently labeled polymer analog together with the mitochondria-specific vital dye label indicated that the carrier did indeed reach mitochondria. The high CoQ10 loading efficiency allowed testing of micelles within a broad concentration range and provided evidence for CoQ10 effectiveness in two different experimental paradigms: oxidative stress and inflammation. Combined results from chemical, analytical, and biological experiments suggest that the new miktoarm-based carrier provides a suitable means of CoQ10 delivery to mitochondria without loss of drug effectiveness. The versatility of the click chemistry used to prepare this new mitochondria-targeting nanocarrier offers a widely applicable, simple, and easily reproducible procedure to deliver drugs to mitochondria or other intracellular organelles.

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Therapeutic use of coenzyme Q₁₀and coenzyme Q₁₀-related compounds and formulations

Cited by 123 publications

References 169 publications

Idebenone Prevents Human Optic Nerve Head Astrocytes From Oxidative Stress, Apoptosis, and Senescence by Stabilizing BAX/Bcl-2 Ratio

Idebenone Prevents Human Optic Nerve Head Astrocytes From Oxidative Stress, Apoptosis, and Senescence by Stabilizing BAX/Bcl-2 Ratio

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Design and Evaluation of Multifunctional Nanocarriers for Selective Delivery of Coenzyme Q10 to Mitochondria

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Therapeutic use of coenzyme Q10and coenzyme Q10-related compounds and formulations

Cited by 123 publications

References 169 publications

Idebenone Prevents Human Optic Nerve Head Astrocytes From Oxidative Stress, Apoptosis, and Senescence by Stabilizing BAX/Bcl-2 Ratio

Idebenone Prevents Human Optic Nerve Head Astrocytes From Oxidative Stress, Apoptosis, and Senescence by Stabilizing BAX/Bcl-2 Ratio

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

Design and Evaluation of Multifunctional Nanocarriers for Selective Delivery of Coenzyme Q10 to Mitochondria

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Product

Resources

About

Therapeutic use of coenzyme Q₁₀and coenzyme Q₁₀-related compounds and formulations