A5070509047- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Coenzyme Q10 studies and effects
- ATP Synthase and ATPases Research
- Advanced battery technologies research
- Biochemical Acid Research Studies
- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- Genetic Neurodegenerative Diseases
- Glycogen Storage Diseases and Myoclonus
- Neurogenetic and Muscular Disorders Research
- Neurological disorders and treatments
- Genomics and Rare Diseases
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- RNA and protein synthesis mechanisms
- Cardiomyopathy and Myosin Studies
- Cholinesterase and Neurodegenerative Diseases
- Diet and metabolism studies
- Muscle metabolism and nutrition
- Alzheimer's disease research and treatments
- Vitamin K Research Studies
- Amino Acid Enzymes and Metabolism
- Cytomegalovirus and herpesvirus research
Columbia University Irving Medical Center
2014-2024
Columbia University
2009-2024
New York Audio Productions (United States)
2015-2016
University Hospital and Clinics
2007
Ludwig-Maximilians-Universität München
2007
Evangelisches Krankenhaus Bielefeld
2007
Hacettepe University
2007
The Neurological Institute
2006
Inserm
2003-2005
Whitehead Institute for Biomedical Research
2005
Parkinson's disease (PD) is a neurodegenerative disorder of uncertain pathogenesis characterized by the loss nigrostriatal dopaminergic neurons, which can be modeled neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Increased expression cyclooxygenase type 2 (COX-2) and production prostaglandin E(2) have been implicated in neurodegeneration several pathological settings. Here we show that COX-2, rate-limiting enzyme synthesis, up-regulated brain neurons both PD MPTP mice. COX-2...
The decrement in dopamine levels exceeds the loss of dopaminergic neurons Parkinson's disease (PD) patients and experimental models PD. This discrepancy is poorly understood may represent an important event pathogenesis Herein, we report that rate-limiting enzyme synthesis, tyrosine hydroxylase (TH), a selective target for nitration following exposure PC12 cells to either peroxynitrite or 1-methyl-4-phenylpyridiniun ion (MPP+). Nitration TH also occurs mouse striatum after MPTP...
Parkinson disease (PD) is a neurodegenerative disorder characterized by loss of the nigrostriatal dopaminergic neurons accompanied deficit in mitochondrial respiration. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin that causes neurodegeneration and reminiscent PD. Here we show infusion ketone body d-beta-hydroxybutyrate (DbetaHB) mice confers partial protection against motor deficits induced MPTP. These effects appear to be mediated complex II-dependent mechanism leads...
Parkinson disease (PD) is a neurodegenerative disorder characterized by loss of the nigrostriatal dopaminergic neurons accompanied deficit in mitochondrial respiration. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin that causes neurodegeneration and reminiscent PD. Here we show infusion ketone body D-β-hydroxybutyrate (DβHB) mice confers partial protection against motor deficits induced MPTP. These effects appear to be mediated complex II–dependent mechanism leads improved...
Coenzyme Q10 (CoQ10) deficiency is an autosomal recessive disorder with heterogenous phenotypic manifestations and genetic background. We describe seven patients from five independent families isolated myopathic phenotype of CoQ10 deficiency. The clinical, histological biochemical presentation our was very homogenous. All presented exercise intolerance, fatigue, proximal myopathy high serum CK. Muscle histology showed lipid accumulation subtle signs mitochondrial myopathy. Biochemical...
Mutations in the copper/zinc superoxide dismutase (mSOD1) gene are associated with a familial form of amyotrophic lateral sclerosis (ALS), and their expression transgenic mice produces an ALS-like syndrome. Recent observations suggest role for inflammatory-related events progression propagation neurodegenerative process ALS. Consistent this view, present study demonstrates that, during course disease, cyclooxygenase type 2 (Cox-2), key enzyme synthesis prostanoids, which potent mediators...
<b><i>Objective:</i></b> To describe a clinical syndrome of cerebellar ataxia associated with muscle coenzyme Q10 (CoQ10) deficiency. <b><i>Background:</i></b> Muscle CoQ10 deficiency has been reported only in few patients mitochondrial encephalomyopathy characterized by 1) recurrent myoglobinuria; 2) brain involvement (seizures, ataxia, mental retardation), and 3) ragged-red fibers lipid storage the biopsy. <b><i>Methods:</i></b> Having found decreased levels from patient unclassified...
Mitochondrialneurogastrointestinalencephalomyopathy (MNGIE) is an autosomal recessive human disease due to mutations in the thymidine phosphorylase (TP) gene. TP enzyme catalyzes reversible phosphorolysis of thymine and 2-deoxy-d-ribose 1-phosphate. We present evidence that metabolism altered MNGIE. activities buffy coats were reduced drastically all 27 MNGIE patients compared with 19 controls. All had much higher plasma levels than normal individuals asymptomatic mutation carriers. In two...
<h3>Background</h3> Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used for the treatment of hypercholesterolemia and coronary heart disease prevention stroke. There have been various adverse effects, most commonly affecting muscle ranging from myalgia to rhabdomyolysis. These effects may be due a Q<sub>10</sub>(CoQ<sub>10</sub>) deficiency because inhibition cholesterol biosynthesis also inhibits synthesis CoQ<sub>10</sub>. <h3>Objective</h3> To measure...
The authors measured coenzyme Q10 (CoQ10) concentration in muscle biopsies from 135 patients with genetically undefined cerebellar ataxia. Thirteen childhood-onset ataxia and atrophy had markedly decreased levels of CoQ10. Associated symptoms included seizures, developmental delay, mental retardation, pyramidal signs. These findings confirm the existence an ataxic presentation CoQ10 deficiency, which may be responsive to supplementation.
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 corticosteroid-resistant nephrotic syndrome in whom progressive encephalomyopathy later developed. CoQ10 was decreased both muscle and fibroblasts. Oral improved the neurologic picture but not renal dysfunction.
Background: Statin drugs (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) reduce the level of cholesterol by inhibiting synthesis mevalonate, an intermediary in biosynthetic pathway.Use statin has been associated with a variety skeletal muscle-related complaints.Coenzyme Q 10 (CoQ ), component mitochondrial respiratory chain, is also synthesized from and decreased muscle CoQ concentration may have role pathogenesis drug-related myopathy.Objectives: To measure chain enzyme...
Primary muscle coenzyme Q10 (CoQ10) deficiency is an apparently autosomal recessive condition with heterogeneous clinical presentations. Patients these disorders improve CoQ10 supplementation. In a family ataxia and deficiency, analysis of genome-wide microsatellite markers suggested linkage the disease to chromosome 9p13 led identification aprataxin gene (APTX) mutation that causes oculomotor apraxia (AOA1 [MIM606350]). The authors' observations indicate may contribute pathogenesis AOA1.
We aimed to investigate oxidative stress biomarkers in a cross-sectional pilot study of 50 participants with sporadic ALS (SALS) compared 46 control subjects. measured urinary 8-oxodeoxyguanosine (8-oxodG), 15-F2t-isoprostane (IsoP), and plasma protein carbonyl by ELISA methods. also determined if measurement 8-oxodG could be validated against measures from high-pressure liquid chromatography coupled electrochemical detection, the current standard method. found that IsoP levels adjusted for...
Coenzyme Q(10) (CoQ(10)) is essential for electron transport in the mitochondrial respiratory chain and antioxidant defense. Last year, we reported first mutations CoQ(10) biosynthetic genes, COQ2, which encodes 4-parahydroxybenzoate: polyprenyl transferase; PDSS2, subunit 2 of decaprenyl diphosphate synthase. However, pathogenic mechanisms primary deficiency have not been well characterized. In this study, investigated consequence severe on bioenergetics, oxidative stress, defenses cultured...
Coenzyme Q10 (CoQ10) is essential for electron transport in the mitochondrial respiratory chain and antioxidant defense. The relative importance of defects, ROS production, apoptosis pathogenesis CoQ10 deficiency unknown. We determined previously that severe cultured skin fibroblasts harboring COQ2 PDSS2 mutations produces divergent alterations bioenergetics oxidative stress. Here, to better understand deficiency, we have characterized effects varying severities on production cells genetic...
<b><i>Background: </i></b> The mitochondrial DNA (mtDNA) depletion syndrome (MDS) is an autosomal recessive disorder of early childhood characterized by decreased mtDNA copy number in affected tissues. Recently, MDS has been linked to mutations two genes involved deoxyribonucleotide (dNTP) metabolism: thymidine kinase 2 (<i>TK2</i>) and deoxy-guanosine (<i>dGK</i>). Mutations <i>TK2</i> have associated with the myopathic form MDS, <i>dGK</i> hepatoencephalopathic form. <b><i>Objectives: To...
Abstract Mitochondrial DNA depletion syndrome is a clinically heterogeneous group of disorders characterized by reduction in mitochondrial copy number. The recent discovery mutations the deoxyguanosine kinase ( dGK ) gene patients with hepatocerebral form prompted us to screen 21 determine frequency mutations, further characterize clinical spectrum, and correlate genotypes phenotypes. We detected three (14%). One patient had homozygous GATT duplication (nucleotides 763–766), another GT...
Abstract Parkinson's disease (PD) is characterized mainly by a loss of nigrostriatal dopamine neurons. Thus far, the actual physiopathology PD remains uncertain, although recent studies have found decreased activity complex I, one enzymatic units mitochondrial respiratory chain, in various tissues patients. Because most, if not all, patients are treated chronically with levodopa, precursor dopamine, and because we shown previously that catecholamines may alter respiration, assessed effects...
Abstract Testing for common mutations in mitochondrial DNA (mtDNA), including the A3243G MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) mutation, is routinely done isolated from blood. Since blood level of mutation may be low probands even lower asymptomatic or oligosymptomatic maternal relatives, we assessed proportion mutant genomes other accessible tissues. We studied five tissues (leukocytes, skin fibroblasts, hair roots, urinary sediment, cheek mucosa)...
Background : The number of molecular causes MELAS (a syndrome consisting mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) Leigh (LS) has steadily increased.Among these, mutations in the ND5 gene (OMIM 516005) DNA are important, A13513A change emerged as a hotspot.Objective: To describe clinical features, muscle pathological biochemical characteristics, study findings 12 patients harboring G13513A mutation compared with 14 previously described same mutation.Design:...