Therapeutic Effects of Coenzyme Q10 in Neurodegenerative Diseases
Introduction
There is increasing interest in the potential usefulness of coenzyme Q10 (CoQ10) to treat both mitochondrial disorders as well as neurodegenerative diseases such as Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). CoQ10 may also be useful in treating Freidriech's ataxia, which has been shown to be caused by a mutation in the protein frataxin, which is localized to mitochondria. CoQ10 is composed of a quinone ring and a 10-isoprene unit tail and is distributed in all membranes throughout the cell. CoQ10 serves as an important cofactor of the electron transport chain, where it accepts electrons from complexes I and II. It is initially reduced to the semi-ubiquinone radical and then transfers electrons one at a time to complex III of the electron transport chain.1, 2 CoQ10, which is also known as ubiquinone, serves as an important antioxidant in both mitochondria and lipid membranes. It mediates some of its antioxidant effects through interactions with alpha-tocopherol.1, 3
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Effects in the Central Nervous System
The importance of CoQ10 for central nervous system function is corroborated by neuromuscular disease, which occurs in patients who have a CoQ10 deficiency. A report of two sisters included symptoms of encephalopathy, proximal weakness, myoglobinuria, and lactic acidosis.4 Another patient report was that of a 35-year-old woman who developed proximal weakness, premature exertional fatigue, complex partial seizures, and myoglobinuria.5 On muscle biopsy she was found to have reductions in complex
Pharmacokinetics of Orally Administered CoQ10
A number of studies have evaluated the pharmacokinetics of CoQ10 in humans.22, 23, 24, 24, 25 A single oral dose of CoQ10 is followed by two peaks in serum levels. The first peak occurs at approximately 5 to 6 hours and the second, a much smaller peak, occurs approximately 24 hours after the oral dose. The explanation for the second peak has been proposed to be uptake by the liver and subsequent resecretion. Absorption of CoQ10 is improved by inclusion of lipid in the formulation and by taking
The Antioxidant Properties and Effects of CoQ10 Supplementation in Animals
Several studies have shown that oral administration of CoQ10 can produce protection in experimental models of cerebral ischemia or against mitochondrial toxins. These studies, however, have been controversial, since there are reports that CoQ10 administration does not increase levels in either muscle or brain. In young rats, alpha-tocopherol supplementation produced increases in tissue levels of alpha-tocopherol in plasma, liver, kidney, muscle, and brain, however, CoQ10 supplementation
Neuroprotective Effects in Animal Models of Neurodegeneration
CoQ10 administration protects myocardium from ischemia-reperfusion injury and preserves mitochondrial function.58 CoQ10 has been demonstrated to exert neuroprotective effects in animal models of neuronal injury in the central nervous system. Experimental ischemia can be produced by intracerebroventricular administration of the potent vasoconstrictor endothelin. Administration of CoQ10 at a dose of 10āmgā§økg i.p. resulted in a significant attenuation of ATP and glutathione depletion and
The Effects of CoQ10 Supplementation in Patients With Neurodegenerative Diseases
We and others have previously examined a number of aspects of CoQ10 in patients with neurodegenerative diseases. We measured CoQ10 levels in mitochondria isolated from platelets of PD patients.68 We found a significant reduction in CoQ10 levels that directly correlated with decreases in complex I activity. Oral administration of CoQ10 to the PD patients was well tolerated and resulted in dose-dependent significant increases in plasma CoQ10 levels.
We studied the effects of CoQ10 on elevated
Conclusions
CoQ10 administration can increase brain concentrations in mature and older animals. It can also increase brain mitochondrial concentrations. There is substantial evidence that CoQ10 can act in concert with alpha-tocopherol as an antioxidant within mitochondria. CoQ10 administration has been demonstrated to be efficacious in experimental models of neurodegenerative diseases. It is neuroprotective against lesions produced by mitochondrial toxins including malonate, 3-nitropropionic acid and MPTP.
References (82)
- et al.
Free Radic. Biol. Med.
(2000) - et al.
Lancet
(2000) - et al.
Brain Res. Bull.
(2001) Biochim. Biophys. Acta
(1995)- et al.
Neurosci. Lett.
(1994) - et al.
J. Neurol. Sci.
(1997) - et al.
J. Nutr.
(1996) - et al.
J. Nutr.
(2000) - et al.
Mech. Ageing Dev.
(1995) - et al.
Mech. Ageing Dev.
(1985)
Free Radic. Biol. Med.
Free Radic. Biol. Med.
Biochem. Biophys. Res. Commun.
Free Radic. Biol. Med.
Free Radic. Biol. Med.
Arch. Biochem.
Biochim. Biophys. Acta
Free Radic. Biol. Med.
Eur. J. Pharmacol.
Free Radic. Bio. Med.
J. Biol. Chem.
J. Biol. Chem.
Biochem. Biophys. Res. Comm.
Molec. Aspects Med.
J. Biol. Chem.
FEBS Lett.
J. Surg. Res.
Brain Res. Bull.
Neurosci. Lett.
Cell
Neurochem. Int.
Lancet
Biochem. Cell. Biol.
Free Radic. Res.
Proc. Natl. Acad. Sci. USA
Neurology
J. Neurol. Sci.
Neurology
Neurology
Ann. Neurol.
Neurology
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2020, Brain ResearchCitation Excerpt :CoQ10 supplementation in rats increases endogenous CoQ10 content in the brain and brain mitochondria (Matthews et al., 1998; Beal, 2004). CoQ10 acts as an antioxidant against oxidative stress (Somayajulu et al., 2005; Beal, 2004; Lenaz et al., 1999) and can regenerate other potent antioxidants (Lass and Sohal, 1998). It has been reported that CoQ10 up-regulates mitochondrial function (Beal et al., 1994) and also improves cognitive performances (Mcdonald et al., 2005).
Coenzyme Q10 treatment improved visual field after homonymous quadrantanopia caused by occipital lobe infarction
2019, American Journal of Ophthalmology Case ReportsCitation Excerpt :CoQ10, the most common coenzyme Q in humans, is an essential cofactor of the electron transport chain and acts by maintaining the mitochondrial membrane potential, supporting ATP synthesis and inhibiting reactive oxygen species generation for protecting neuronal cells against oxidative stress in neurodegenerative diseases.23,24 Various mechanisms for the beneficial effects of CoQ10 have been suggested including its neuroprotective role, which underlying pathways may involve a dual function, acting as a free radical scavenger and activating the mitochondrial function.25,26 Pretreatment with CoQ10 may protect neuronal cells against oxidative stress stabilizing the mitochondrial membrane and reduced the amount of mitochondrial reactive oxidative species generation.22,27
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2011, Toxicology and Applied PharmacologyCitation Excerpt :CoQ10 has been used to treat a number of human medical conditions, the most prominent of which are mitochondrial disorders, and is most beneficial where there is an inherited deficiency of CoQ10 (Chan et al., 1999; Di Giovanni et al., 2001; Ihara et al., 1989; Nishikawa et al., 1989; Shults, 2002; Tomasetti et al., 1999). CoQ10 is effective in slowing the progression of neurological disease (Beal, 2004a; Shults, 2002). Coenzyme Q10, which is also known as ubiquinone is the predominant form of Coenzyme Q10 in humans.