coenzyme-q10 and Neuromuscular-Diseases

Coenzyme Q

Topics: Biological Availability; Dietary Supplements; Humans; Migraine Disorders; Neoplasms; Neurodegenerative Diseases; Neuromuscular Diseases; Quality of Life; Ubiquinone

Coenzyme Q10 (CoQ10, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of CoQ10 in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in CoQ10 status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of CoQ10 biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of CoQ10 status following HMG-Coa reductase inhibitor (statins) treatment has be implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. CoQ10 and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of CoQ10, as well as the rationale and the role in clinical practice of CoQ10 supplementation in different neurological and muscular diseases, from primary CoQ10 deficiency to neurodegenerative disorders. We also briefly report a case of the myopathic form of CoQ10 deficiency.

Topics: Animals; Humans; Mitochondrial Diseases; Neurodegenerative Diseases; Neuromuscular Diseases; Ubiquinone

Coenzyme Q (CoQ) is an essential component of the respiratory chain but also participates in other mitochondrial functions such as regulation of the transition pore and uncoupling proteins. Furthermore, this compound is a specific substrate for enzymes of the fatty acids beta-oxidation pathway and pyrimidine nucleotide biosynthesis. Furthermore, CoQ is an antioxidant that acts in all cellular membranes and lipoproteins. A complex of at least ten nuclear (COQ) genes encoded proteins synthesizes CoQ but its regulation is unknown. Since 1989, a growing number of patients with multisystemic mitochondrial disorders and neuromuscular disorders showing deficiencies of CoQ have been identified. CoQ deficiency caused by mutation(s) in any of the COQ genes is designated primary deficiency. Other patients have displayed other genetic defects independent on the CoQ biosynthesis pathway, and are considered to have secondary deficiencies. This review updates the clinical and molecular aspects of both types of CoQ deficiencies and proposes new approaches to understanding their molecular bases.

Topics: Humans; Mitochondrial Diseases; Neuromuscular Diseases; Ubiquinone

This review considers primary mitochondrial diseases affecting the respiratory chain. As diseases due to mitochondrial DNA defects defy traditional anatomical classifications, we have not limited our discussion to neuromuscular disorders, but have extended it to include mitochondrial encephalomyopathies. Primary mitochondrial diseases can be due to mutations in either the nuclear or the mitochondrial genome. Nuclear mutations can affect (i) genes encoding enzymatic or structural mitochondrial proteins; (ii) translocases; (iii) mitochondrial protein importation; and (iv) intergenomic signaling. We review briefly recent molecular data and outstanding questions regarding these mendelian disorders, with special emphasis on cytochrome c oxidase deficiency and coenzyme Q10 deficiency. Mitochondrial DNA mutations fall into three main categories: (i) sporadic rearrangements (deletions/duplications); (ii) maternally inherited rearrangements (duplications); and (iii) maternally inherited point mutations. We summarize the most common clinical presentations and discuss pathogenic mechanisms, which remain largely elusive. Uncertainties about pathogenesis extend to the process of cell death, although excitotoxicity in neurons and apoptosis in muscle seem to have important roles.

Topics: Animals; Coenzymes; Cytochrome-c Oxidase Deficiency; DNA, Mitochondrial; Electron Transport Complex IV; Gene Deletion; Humans; Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Multigene Family; Neuromuscular Diseases; Point Mutation; Ubiquinone

Coenzyme Q10 was administered under placebo controlled blinded crossover conditions to six subjects suffering from type 3 3-methylglutaconic aciduria ('optic atrophy plus'), following a report of benefit. Despite attainment of high plasma levels of coenzyme Q10, no clinical benefit was observed and there was no diminution of urinary excretion of 3-methylglutaconic acid.

Topics: Administration, Oral; Adolescent; Adult; Child; Coenzymes; Cross-Over Studies; Female; Glutarates; Humans; Male; Movement Disorders; Neuromuscular Diseases; Optic Atrophy; Single-Blind Method; Treatment Failure; Ubiquinone; Visual Acuity

Near-infrared spectrometry (NIRS) is a well-known method used to measure in vivo tissue oxygenation and hemodynamics. This method is used to derive relative measures of hemoglobin (Hb) + myoglobin (Mb) oxygenation and total Hb (tHb) accumulation from measurements of optical attenuation at discrete wavelengths. We present the design and validation of a new NIRS oxygenation analyzer for the measurement of muscle oxygenation kinetics. This design optimizes optical sensitivity and detector wavelength flexibility while minimizing component and construction costs. Using in vitro validations, we demonstrate 1) general optical linearity, 2) system stability, and 3) measurement accuracy for isolated Hb. Using in vivo validations, we demonstrate 1) expected oxygenation changes during ischemia and reactive hyperemia, 2) expected oxygenation changes during muscle exercise, 3) a close correlation between changes in oxyhemoglobin and oxymyoglobin and changes in deoxyhemoglobin and deoxymyoglobin and limb volume by venous occlusion plethysmography, and 4) a minimal contribution from movement artifact on the detected signals. We also demonstrate the ability of this system to detect abnormal patterns of tissue oxygenation in a well-characterized patient with a deficiency of skeletal muscle coenzyme Q(10). We conclude that this is a valid system design for the precise, accurate, and sensitive detection of changes in bulk skeletal muscle oxygenation, can be constructed economically, and can be used diagnostically in patients with disorders of skeletal muscle energy metabolism.

Topics: Coenzymes; Electronics; Equipment Design; Exercise; Hemoglobins; Humans; Hyperemia; Ischemia; Kinetics; Metabolism, Inborn Errors; Movement; Muscle, Skeletal; Myoglobin; Neuromuscular Diseases; Oxygen; Oxygen Consumption; Plethysmography; Reproducibility of Results; Sensitivity and Specificity; Spectroscopy, Near-Infrared; Ubiquinone

Coenzyme Q10 (CoQ) content was measured in isolated muscle mitochondria from 25 patients with mitochondrial encephalomyopathies (MEM), most of whom had mitochondrial DNA mutations. The CoQ level was significantly lower in MEM patients than in controls. CoQ levels varied widely from patient to patient, especially in those with chronic progressive external ophthalmoplegia including Kearns-Sayre syndrome, which may explain, at least in part, the variable response of patients to CoQ administration.

Topics: Adolescent; Adult; Child; Coenzymes; DNA, Mitochondrial; Female; Humans; Male; Middle Aged; Mitochondria, Muscle; Muscular Diseases; Mutation; Neuromuscular Diseases; Ubiquinone

Topics: Acidosis, Lactic; Benzoquinones; Brain Diseases, Metabolic; Coenzymes; Female; Humans; Middle Aged; Mitochondria, Muscle; Neuromuscular Diseases; Quinones; Syndrome; Ubiquinone