coenzyme-q10 and Nervous-System-Diseases

Coenzyme Q10 (CoQ10), a lipophilic substituted benzoquinone, is present in animal and plant cells. It is endogenously synthetized in every cell and involved in a variety of cellular processes. CoQ10 is an obligatory component of the respiratory chain in inner mitochondrial membrane. In addition, the presence of CoQ10 in all cellular membranes and in blood. It is the only endogenous lipid antioxidant. Moreover, it is an essential factor for uncoupling protein and controls the permeability transition pore in mitochondria. It also participates in extramitochondrial electron transport and controls membrane physicochemical properties. CoQ10 effects on gene expression might affect the overall metabolism. Primary changes in the energetic and antioxidant functions can explain its remedial effects. CoQ10 supplementation is safe and well-tolerated, even at high doses. CoQ10 does not cause any serious adverse effects in humans or experimental animals. New preparations of CoQ10 that are less hydrophobic and structural derivatives, like idebenone and MitoQ, are being developed to increase absorption and tissue distribution. The review aims to summarize clinical and experimental effects of CoQ10 supplementations in some neurological diseases such as migraine, Parkinson´s disease, Huntington´s disease, Alzheimer´s disease, amyotrophic lateral sclerosis, Friedreich´s ataxia or multiple sclerosis. Cardiovascular hypertension was included because of its central mechanisms controlling blood pressure in the brainstem rostral ventrolateral medulla and hypothalamic paraventricular nucleus. In conclusion, it seems reasonable to recommend CoQ10 as adjunct to conventional therapy in some cases. However, sometimes CoQ10 supplementations are more efficient in animal models of diseases than in human patients (e.g. Parkinson´s disease) or rather vague (e.g. Friedreich´s ataxia or amyotrophic lateral sclerosis).

Topics: Animals; Antioxidants; Electron Transport; Humans; Mitochondria; Mitochondrial Diseases; Nervous System Diseases; Ubiquinone

Topics: Humans; Mental Disorders; Mitochondria; Nervous System Diseases; Oxidative Stress; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome; Ubiquinone; Vitamins

Coenzyme Q10 (CoQ10) is critical for the cell power supply in mitochondria. CoQ10 shuttles electrons from complexes I and II to complex III, and can be anti-oxdiative. Neurons require high energy for synaptic transmission and therefore the mitochondria dysfunction often leads to severe neuronal degeneration, as observed in many neurological disorders. CoQ10 supplementation has been widely used to treat aging, stroke, neuromuscular diseases, Alzheimer's disease, Parkinson's disease, progressive supranuclear palsy, autosomal recessive cerebellar ataxias, Huntington's disease and amyotrophic lateral sclerosis. Here we discuss a large number of preclinical and clinical trials for CoQ10 to elucidate the mechanisms underlying CoQ10 therapy. The rational applications as a therapeutic agent in neurological disorders are discussed.

Topics: Animals; Biomedical Research; Electron Transport Chain Complex Proteins; Humans; Mitochondria; Nervous System Diseases; Neurons; Neuroprotective Agents; Ubiquinone

Coenzyme Q10 (CoQ10) plays a pivotal role in oxidative phosphorylation (OXPHOS) as it distributes electrons between the various dehydrogenases and the cytochrome segments of the respiratory chain. Primary coenzyme Q10 deficiency is a rare, but possibly treatable, autosomal recessive condition with four major clinical presentations, an encephalomyopathic form, a generalized infantile variant with severe encephalopathy and renal disease, a myopathic form and an ataxic form. The diagnosis of ubiquinone deficiency is supported by respiratory chain analysis and eventually by the quantification of CoQ10 in patient tissues. We review here the infantile and pediatric quinone deficiency diseases as well as the clinical improvement after oral CoQ10 therapy. The clinical heterogeneity of ubiquinone deficiency is suggestive of a genetic heterogeneity that should be related to the large number of enzymes, and corresponding genes, involved in ubiquinone biosynthesis.

Topics: Child; Child, Preschool; Coenzymes; Humans; Infant; Infant, Newborn; Mitochondria; Models, Biological; Nervous System Diseases; Oxygen; Oxygen Consumption; Succinates; Ubiquinone

Topics: Amyotrophic Lateral Sclerosis; Child; Clinical Trials as Topic; Coenzymes; Friedreich Ataxia; Heart Arrest; Humans; Huntington Disease; Mitochondrial Diseases; Nervous System Diseases; Parkinson Disease; Ubiquinone

Coenzyme Q10 (Q10) is available as an over-the-counter dietary supplement in the United States. While its use could be considered a form of alternative therapy, the medical profession has embraced the use of Q10 in specific disease states, including a series of neurologic and muscular diseases. Clinical laboratory monitoring is available for measurement of total Q10 in plasma and tissue and for measurement of redox status, ie, the ratio of reduced and oxidized forms of Q10. Many published studies have been anecdotal, in part owing to the rarity of some diseases involved. Unfortunately, many studies do not report Q10 levels, and, thus, the relationship of clinical response to Q10 concentration in plasma frequently is not discernible. Consistent laboratory monitoring of patients treated with this compound would help ease interpretation of the results of the treatment, especially because so many formulations of Q10 exist in the marketplace, each with its own bioavailability characteristics. Q10 has an enviable safety profile and, thus, is ideal to study as an adjunct to more conventional therapy. Defining patient subpopulations and characteristics that predict benefit from exogenous Q10 and defining therapeutic ranges for those particular applications are major challenges in this field.

Topics: Coenzymes; Epilepsies, Myoclonic; Friedreich Ataxia; Humans; Huntington Disease; Kearns-Sayre Syndrome; Mitochondrial Encephalomyopathies; Muscular Diseases; Nervous System Diseases; Parkinson Disease; Ubiquinone

The concepts of energy dysregulation and oxidative stress and their complicated interdependence have rapidly evolved to assume primary importance in understanding the pathophysiology of numerous neurological disorders. Therefore, neuroprotective strategies addressing specific bioenergetic defects hold particular promise in the treatment of these conditions (i.e., amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, Friedreich's ataxia, mitochondrial cytopathies and other neuromuscular diseases), all of which, to some extent, share 'the final common pathway' leading to cell death through either necrosis or apoptosis. Compounds such as creatine monohydrate and coenzyme Q(10) offer substantial neuroprotection against ischaemia, trauma, oxidative damage and neurotoxins. Miscellaneous agents, including alpha-lipoic acid, beta-OH-beta-methylbutyrate, riboflavin and nicotinamide, have also been shown to improve various metabolic parameters in brain and/or muscle. This review will highlight the biological function of each of the above mentioned compounds followed by a discussion of their utility in animal models and human neurological disease. The balance of this work will be comprised of discussions on the therapeutic applications of creatine and coenzyme Q(10).

Topics: Amyotrophic Lateral Sclerosis; Animals; Coenzymes; Creatine; Disease Models, Animal; Energy Metabolism; Humans; Huntington Disease; Nervous System Diseases; Neuroprotective Agents; Ubiquinone

The manual workers of the gas-and-oil extraction industry are exposed to hostile environmental and occupational conditions, resulting in elevated mortality and disability, due to chronic neurological and cardiovascular diseases. We evaluated the degree of oxidative stress, often associated with these pathological features, in the blood of manual and office employees of Russian Siberian extraction plants, and their psycho-physiological conditions. Results showed increased levels of spontaneous (p < 0.05) and PMA-activated (p < 0.01) luminol-dependent chemiluminescence (LDCL) in the white blood cells (WBC), and decreased peroxynitrite levels (p < 0.05) in the group of manual workers, and less markedly in the clerks and technicians working on spot, vs. a control group of city clerks. Superoxide release by WBC, and plasma/WBC membrane ubiquinol levels did not display major differences in the three groups. A relevant percentage of manual/office workers of extraction platforms presented impaired cardiovascular and neurological functions. The short term administration of a nutraceutical formulation based on coenzyme10, vitamin E, selenium, methionine and phospholipids led to significant improvement of cardiovascular parameters and psycho-emotional status, consistent with the normalization of LDCL and peroxynitrite production by WBC, with a good compliance to treatment confirmed by the increased blood levels of ubiquinol.

Topics: Adult; Cardiovascular Diseases; Coenzymes; Dietary Supplements; Emotions; Environment; Female; Humans; Industrial Oils; Leukocytes; Luminescent Measurements; Luminol; Male; Methionine; Middle Aged; Nervous System Diseases; Occupational Exposure; Oxidative Stress; Peroxynitrous Acid; Petroleum; Phospholipids; Russia; Selenium; Siberia; Superoxides; Tetradecanoylphorbol Acetate; Ubiquinone; Vitamin E

Background The physiopathologies of many neurologic diseases are characterized by related biochemical dysfunctions that could be explored as drug targets. This study evaluated the effect of a methanol leaf extract of Antiaris africana (MEA) on critical bioindices of Parkinsonism and related neurologic dysfunctions in rats with rotenone-induced neurotoxicity. Methods Animals were administered 50 or 100 mg/kg MEA for 14 consecutive days. Rotenone (1.5 mg/kg) was administered three times per day on days 13 and 14. Coenzyme Q10 (5 mg/kg) was the reference drug. Complex I activity, dopamine level, activities of acetylcholinesterase, myeloperoxidase, Na+/K+ ATPase and glutamine synthetase, as well as oxidative stress indices were evaluated at the end of the period of treatment. Results Rotenone-intoxicated group showed disruption of complex 1 activity, dopamine level, and glutamine synthetase activity with negative alterations to activities of acetylcholinesterase, myeloperoxidase, and Na+/K+ ATPase as well as heightened cerebral oxidative stress. MEA restored brain mitochondria functionality, mitigated altered neurochemical integrity, and ameliorated cerebral oxidative stress occasioned by rotenone neurotoxicity. The activity of A. Africana was comparable with that of 5 mg/kg coenzyme Q10. Conclusions These results indicated that A. africana displayed therapeutic potential against Parkinsonism and related neurologic dysfunctions and support its ethnobotanical use for the treatment of neurologic disorders.

Topics: Acetylcholinesterase; Animals; Antiaris; Dopamine; Glutamate-Ammonia Ligase; Male; Mitochondria; Nervous System Diseases; Neuroprotective Agents; Oxidative Stress; Parkinsonian Disorders; Peroxidase; Plant Extracts; Rats; Rats, Wistar; Rotenone; Sodium-Potassium-Exchanging ATPase; Ubiquinone

Identifying diseases displaying chronic low plasma Coenzyme Q

Topics: Adolescent; Adult; Case-Control Studies; Child; Child, Preschool; Chromatography, High Pressure Liquid; Female; Humans; Infant; Infant, Newborn; Male; Metabolism, Inborn Errors; Mucopolysaccharidoses; Mutation; Nervous System Diseases; Phenylketonurias; Retrospective Studies; Sequence Analysis, DNA; Ubiquinone; Young Adult

Coenzyme Q10 (CoQ10) crosses the blood-brain barrier when administered intravenously and accumulates in the brain. In this study, we investigated whether CoQ10 protects against ischemia-reperfusion injury by measuring neurological function and brain infarct volumes in a rat model of transient focal cerebral ischemia. In male Wistar rats, we performed transient middle cerebral artery occlusion (tMCAO) for 60 minutes, followed by reperfusion for 24 hours or 7 days. Forty-five minutes after the onset of occlusion (or 15 minutes before reperfusion), rats received a single intravenous injection of solubilized CoQ10 (30 mg·mL(-1)·kg(-1)) or saline (2 mL/kg). Sensory and motor function scores and body weights were obtained before the rats were killed by decapitation, and brain infarct volumes were calculated using tetrazolium chloride staining. CoQ10 brain levels were measured by high-performance liquid chromatography with electrochemical detection. CoQ10 significantly improved neurological behavior and reduced weight loss up to 7 days after tMCAO (P < 0.05). Furthermore, CoQ10 reduced cerebral infarct volumes by 67% at 24 hours after tMCAO and 35% at 7 days (P < 0.05). Cerebral ischemia resulted in a significant reduction in endogenous CoQ10 in both hemispheres (P < 0.05). However, intravenous injection of solubilized CoQ10 resulted in its increase in both hemispheres at 24 hours and in the contralateral hemisphere at 7 days (P < 0.05). Our results demonstrate that CoQ10 is a robust neuroprotective agent against ischemia-reperfusion brain injury in rats, improving both functional and morphological indices of brain damage.

Topics: Animals; Brain Ischemia; Cerebral Infarction; Injections, Intravenous; Male; Nervous System Diseases; Neuroprotective Agents; Rats; Rats, Wistar; Treatment Outcome; Ubiquinone

Topics: Coenzymes; Humans; Nervous System Diseases; Ubiquinone

Neuronal death in neurodegenerative diseases may involve energy impairment leading to secondary excitotoxicity, and free radical generation. Potential therapies for the treatment of neurodegenerative diseases therefore include glutamate release blockers, excitatory amino acid receptor antagonists, agents that improve mitochondrial function, and free radical scavengers. In the present study we examined whether these strategies either alone or in combination had neuroprotective effects against striatal lesions produced by mitochondrial toxins. The glutamate release blockers lamotrigine and BW1003C87 significantly attenuated lesions produced by intrastriatal administration of 1-methyl-4-phenylpyridinium. Lamotrigine significantly attenuated lesions produced by systemic administration of 3-nitropropionic acid. Memantine, an N-methyl-D-aspartate antagonist, protected against malonate induced striatal lesions. We previously found that coenzyme Q10 and nicotinamide, and the free radical spin trap n-tert-butyl-alpha-(2-sulfophenyl)-nitrone (S-PBN) dose-dependently protect against lesions produced by intrastriatal injection of malonate. In the present study we found that the combination of MK-801 (dizocipiline) with coenzyme Q10 exerted additive neuroprotective effects against malonate. Lamotrigine with coenzyme Q10 was more effective than coenzyme Q10 alone. The combination of nicotinamide with S-PBN was more effective than nicotinamide alone. These results provide further evidence that glutamate release inhibitors and N-acetyl-D-aspartate antagonists can protect against secondary excitotoxic lesions in vivo. Furthermore, they show that combinations of agents which act at sequential steps in the neurodegenerative process can produce additive neuroprotective effects. These findings suggest that combinations of therapies to improve mitochondrial function, to block excitotoxicity and to scavenge free radicals may be useful in treating neurodegenerative diseases.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Anticonvulsants; Coenzymes; Cyclic N-Oxides; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Free Radicals; Lamotrigine; Male; Malonates; Memantine; Mitochondria; Nervous System Diseases; Neuroprotective Agents; Neurotoxins; Niacinamide; Nitro Compounds; Nitrogen Oxides; Propionates; Pyrimidines; Rats; Rats, Sprague-Dawley; Spin Labels; Thallium; Triazines; Ubiquinone