coenzyme-q10 and Atrophy

Coenzyme Q(10) (CoQ(10)) is an essential electron carrier in the mitochondrial respiratory chain and an important antioxidant. Deficiency of CoQ(10) is a clinically and molecularly heterogeneous syndrome, which, to date, has been found to be autosomal recessive in inheritance and generally responsive to CoQ(10) supplementation. CoQ(10) deficiency has been associated with five major clinical phenotypes: (1) encephalomyopathy, (2) severe infantile multisystemic disease, (3) cerebellar ataxia, (4) isolated myopathy, and (5) nephrotic syndrome. In a few patients, pathogenic mutations have been identified in genes involved in the biosynthesis of CoQ(10) (primary CoQ(10) deficiencies) or in genes not directly related to CoQ(10) biosynthesis (secondary CoQ(10) deficiencies). Respiratory chain defects, ROS production, and apoptosis contribute to the pathogenesis of primary CoQ(10) deficiencies. In vitro and in vivo studies are necessary to further understand the pathogenesis of the disease and to develop more effective therapies.

Topics: Atrophy; Cerebellum; Child; Chromosome Aberrations; Developmental Disabilities; Disease Progression; DNA Mutational Analysis; Genes, Recessive; Humans; Infant, Newborn; Kidney Diseases; Kidney Glomerulus; Mitochondrial Diseases; Mitochondrial Encephalomyopathies; Mitochondrial Myopathies; Spinocerebellar Degenerations; Ubiquinone

Coenzyme Q(10) (CoQ) deficiency is an autosomal recessive disorder presenting five phenotypes: a myopathic form, a severe infantile neurological syndrome associated with nephritic syndrome, an ataxic variant, Leigh syndrome and a pure myopathic form. The third is the most common phenotype related with CoQ deficiency and it will be the focus of this review. This new syndrome presents muscle CoQ deficiency associated with cerebellar ataxia and cerebellar atrophy as the main neurological signs. Biochemically, the hallmark of CoQ deficiency syndrome is a decreased CoQ concentration in muscle and/or fibroblasts. There is no molecular evidence of the enzyme or gene involved in primary CoQ deficiencies associated with cerebellar ataxia, although recently a family has been reported with mutations at COQ2 gene who present a distinct phenotype. Patients with primary CoQ deficiency may benefit from CoQ supplementation, although the clinical response to this therapy varies even among patients with similar phenotypes. Some present an excellent response to CoQ while others show only a partial improvement of some symptoms and signs. CoQ deficiency is the mitochondrial encephalomyopathy with the best clinical response to CoQ supplementation, highlighting the importance of an early identification of this disorder.

Topics: Alkyl and Aryl Transferases; Atrophy; Cerebellar Ataxia; Cerebellum; Coenzymes; Genetic Predisposition to Disease; Humans; Mitochondria; Mitochondrial Diseases; Ubiquinone

Multiple-system atrophy (MSA) is a neurodegenerative disease characterized by autonomic failure with various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. We previously reported that functionally impaired variants of COQ2, which encodes an essential enzyme in the biosynthetic pathway of coenzyme Q10, are associated with MSA. Here, we report functional deficiencies in mitochondrial respiration and the antioxidative system in induced pluripotent stem cell (iPSC)-derived neurons from an MSA patient with compound heterozygous COQ2 mutations. The functional deficiencies were rescued by site-specific CRISPR/Cas9-mediated gene corrections. We also report an increase in apoptosis of iPSC-derived neurons from MSA patients. Coenzyme Q10 reduced apoptosis of neurons from the MSA patient with compound heterozygous COQ2 mutations. Our results reveal that cellular dysfunctions attributable to decreased coenzyme Q10 levels are related to neuronal death in MSA, particularly in patients with COQ2 variants, and may contribute to the development of therapy using coenzyme Q10 supplementation.

Topics: Adult; Alkyl and Aryl Transferases; Amino Acid Sequence; Atrophy; Base Sequence; Female; Humans; Induced Pluripotent Stem Cells; Male; Middle Aged; Mitochondria; Multiple System Atrophy; Mutation; Neurons; Ubiquinone

To evaluate protective effect of coenzyme Q10 (CoQ10) in lacrimal glands against high-dose radioactive iodine (RAI)-associated oxidative damage.. Thirty Wistar albino rats were randomly divided into three groups. Group 1 was the control group. Group 2 received 3 mCi/kg RAI via gastric gavage but no medication. Group 3 received 3 mCi/kg RAI via gastric gavage and 30 mg/kg/day CoQ10 intraperitoneally. CoQ10 was started at day one just before RAI administration and continued for five days. Seven days after RAI therapy, the animals were anesthetized and decapitated. Intraorbital (IG), extraorbital (EG), and Harderian (HG) lacrimal glands were removed bilaterally for histopathological and tissue cytokine level assessments.. Abnormal lobular pattern, acinar fibrosis, lipofuscin-like accumulations, perivascular infiltration, cell size variation, abnormal cell outlines, irregular nucleus shapes in all lacrimal gland types (p < 0.05 for each), periductal fibrosis, periductal and periacinar fibrosis in EG (p = 0.01, 0.044, respectively) and in HG (p = 0.036, 0.044, respectively), periductal infiltration in HG (p = 0.039) and IG (p = 0.029), acinar atrophy in EG (p = 0.044), and cell shape variation in IG (p = 0.036) were observed more frequently in group 2 than in other groups. RAI caused significant increase in TNF-α, IL-6, nuclear factor kappa B, and total oxidant status, and decrease in IL-2, IL-10, and total antioxidant status levels (p < 0.05 for each). Addition of CoQ10 decreased all cytokine levels, increased nuclear factor kappa B levels more, and increased total antioxidant status levels significantly (p < 0.05 for each).. RAI administration causes prominent inflammatory response in lacrimal glands. Addition of CoQ10 ameliorates the oxidative damage and protects lacrimal glands both in histopathological and tissue cytokine level assessments. Protection of lacrimal glands against oxidative damage may become a new era of CoQ10 use in the future.

Topics: Animals; Atrophy; Cytokines; Dry Eye Syndromes; Fibrosis; Iodine Radioisotopes; Lacrimal Apparatus Diseases; Oxidative Stress; Radiation Injuries, Experimental; Rats; Rats, Wistar; Ubiquinone; Vitamins

We tested the hypotheses that supplemental intake of the diet supplement Coenzyme Q10 (CoQ10) could delay brain atrophy in double transgenic amyloid precursor protein (APP) / presenilin 1 (PS1), single transgenic APP and PS1 as well as wild type mice by volume MR image in vivo. One hundred and twelve mice (28 APP/PS1, 28 APP, 28 PS1 and 28 wild types) were studied. Half of each genotype group (n = 14 per group) was treated with CoQ10 2400 mg/kg/day, and the other half with placebo for 60 days. Magnetic resonance (MR) images were used to obtain the volumes of the hemispheres and hippocampi. APP / PS1, APP, PS1 and wild type mice treated with CoQ10 exhibited significantly less atrophy in hemisphere and hippocampus than those receiving placebo. The neuro-protective effect of the CoQ10 on hemispheric volume, and hippocampal volume was related to genotype; greater in APP/PS1 than APP and PS1 mice and less in wild type mice. Our result indicated that CoQ10 may have therapeutic potential in the prevention and treatment of MCI and AD.

Topics: Aging; Animals; Antioxidants; Atrophy; Brain; Cerebrum; Cognition Disorders; Female; Free Radical Scavengers; Hippocampus; Magnetic Resonance Imaging; Male; Mice; Mice, Transgenic; Presenilin-1; Serum Amyloid A Protein; Ubiquinone

Coenzyme Q10 (CoQ10) deficiency has been associated with various clinical phenotypes, including an infantile multisystem disorder. The authors report a 33-month-old boy who presented with corticosteroid-resistant nephrotic syndrome in whom progressive encephalomyopathy later developed. CoQ10 was decreased both in muscle and in fibroblasts. Oral CoQ10 improved the neurologic picture but not the renal dysfunction.

Topics: Atrophy; Brain; Child, Preschool; Coenzymes; Creatinine; Disease Progression; Early Diagnosis; Electron Transport; Female; Humans; Infant; Kidney Diseases; Magnetic Resonance Imaging; Male; Mitochondria; Mitochondrial Encephalomyopathies; Muscle, Skeletal; Recovery of Function; Treatment Outcome; Ubiquinone