Elsevier

Methods in Enzymology

Volume 382, 2004, Pages 473-487
Methods in Enzymology

Therapeutic Effects of Coenzyme Q10 in Neurodegenerative Diseases

https://doi.org/10.1016/S0076-6879(04)82026-3Get rights and content

Publisher Summary

This chapter analyzes the therapeutic effects of coenzyme Q10 (CoQ10) in neurodegenerative diseases. There is increasing interest in the potential usefulness of 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 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 alphatocopherol 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. CoQ10 extends survival in a transgenic mouse model of ALS, and it extends survival and exerts significant neuroprotective effects in a transgenic mouse model of HD. CoQ10 and idebenone appear to be promising for treatment of Friedriech's ataxia. Initial clinical trials in both HD and PD have shown beneficial effects. The initial results of utilizing CoQ10 administration for treatment of neurodegenerative disease appear promising as a treatment to slow the inexorable progression of these disorders.

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

Section snippets

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 10ā€ˆmgā§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)

  • G. Dallner et al.

    Free Radic. Biol. Med.

    (2000)
  • A. Rotig et al.

    Lancet

    (2000)
  • G. Siciliano et al.

    Brain Res. Bull.

    (2001)
  • P.L. Peterson

    Biochim. Biophys. Acta

    (1995)
  • V. Bruno et al.

    Neurosci. Lett.

    (1994)
  • P. Cortelli et al.

    J. Neurol. Sci.

    (1997)
  • Y. Zhang et al.

    J. Nutr.

    (1996)
  • W.H. Ibrahim et al.

    J. Nutr.

    (2000)
  • M. Battino et al.

    Mech. Ageing Dev.

    (1995)
  • R.E. Beyer et al.

    Mech. Ageing Dev.

    (1985)
  • L.K. Kwong et al.

    Free Radic. Biol. Med.

    (2002)
  • M. Bentinger et al.

    Free Radic. Biol. Med.

    (2003)
  • V. Kagan et al.

    Biochem. Biophys. Res. Commun.

    (1990)
  • J.J. Poderoso et al.

    Free Radic. Biol. Med.

    (1999)
  • V.E. Kagan et al.

    Free Radic. Biol. Med.

    (1990)
  • J.J. Maguire et al.

    Arch. Biochem.

    (1992)
  • K. Mukai et al.

    Biochim. Biophys. Acta

    (1993)
  • H. Shi et al.

    Free Radic. Biol. Med.

    (1999)
  • M.E. Gotz et al.

    Eur. J. Pharmacol.

    (1994)
  • M. Tomasetti et al.

    Free Radic. Bio. Med.

    (1999)
  • L. Walter et al.

    J. Biol. Chem.

    (2000)
  • E. Fontaine et al.

    J. Biol. Chem.

    (1998)
  • S. Vadhanavikit et al.

    Biochem. Biophys. Res. Comm.

    (1993)
  • S. Vadhanavikit et al.

    Molec. Aspects Med.

    (1994)
  • L. Xia et al.

    J. Biol. Chem.

    (2003)
  • J.M. Olsson et al.

    FEBS Lett.

    (1999)
  • J.A. Crestanello et al.

    J. Surg. Res.

    (2002)
  • R.P. Ostrowski

    Brain Res. Bull.

    (2000)
  • E. Brouillet et al.

    Neurosci. Lett.

    (1994)
  • L. Mangiarini et al.

    Cell

    (1996)
  • J. Kaplan

    Neurochem. Int.

    (2002)
  • P. Rustin et al.

    Lancet

    (1999)
  • R.E. Bayer

    Biochem. Cell. Biol.

    (1992)
  • H. Noack et al.

    Free Radic. Res.

    (1994)
  • S. Ogasahara et al.

    Proc. Natl. Acad. Sci. USA

    (1989)
  • S.C. Sobereira et al.

    Neurology

    (1997)
  • E. Boieter et al.

    J. Neurol. Sci.

    (1998)
  • O. Musumeci et al.

    Neurology

    (2001)
  • S. Di Giovanni et al.

    Neurology

    (2001)
  • L. Van Maldergem et al.

    Ann. Neurol.

    (2002)
  • S. Ogasahara et al.

    Neurology

    (1985)
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