Neuroinflammatory and oxidative stress phenomena in MPS IIIA mouse model: the positive effect of long-term aspirin treatment.


:Sanfilippo disease (MPS IIIA) is an autosomal recessive lysosomal storage disorder resulting from sulfamidase deficiency, which is characterized by severe neurological impairment. Various tissues of MPS IIIA mice accumulate undegraded glycosaminoglycans and mimic the human neurodegenerative disorder, and are an excellent tool to both delineate disease pathogenesis and test potential therapies. The relationship between abnormal glycosaminoglycan storage and neurodysfunction remains ill defined. Pathways such as inflammation or oxidative stress have been highlighted in many neurodegenerative disorders, including lysosomal storage diseases, as major components of the neuropathology. By using quantitative polymerase chain reaction, we have compared the expression of selected genes in normal and MPS IIIA mouse cerebral tissues, focusing on inflammation, apoptosis and oxidative stress-related genes. We have identified several genes strongly over-expressed in the central nervous system of a MPS IIIA mouse, reflecting a neurological deterioration state. We have used these genes as markers to follow-up a long-term aspirin treatment. Aspirin treatment led to the normalization of inflammation- and oxidative stress-related mRNA levels in treated MPS IIIA mouse brains. A biochemical correction of an oxidative stress phenomenon both in the brain and peripheral organs of treated MPS IIIA mice was also obtained. These results suggest that anti-inflammatory intervention may be of potential benefit in MPS IIIA disease.


Mol Genet Metab


Arfi A,Richard M,Gandolphe C,Bonnefont-Rousselot D,Thérond P,Scherman D




Has Abstract


2011-05-01 00:00:00














  • First characterization of a large deletion of the PDHA 1 gene.

    abstract::Pyruvate dehydrogenase complex (PDC) deficiency is one of the major recognized causes of congenital lactic acidosis. The most common form is due to PDHA 1 gene (Xp22.12) defects. Here, we report the case of a Polynesian girl presenting with delayed neurological development, cortical atrophy, and posterior corpus callo...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Brivet M,Moutard ML,Zater M,Venet L,Chenel C,Mine M,Legrand A

    更新日期:2005-12-01 00:00:00

  • ELMO1 variants and susceptibility to diabetic nephropathy in American Indians.

    abstract::Variants in the engulfment and cell motility 1 gene, ELMO1, have previously been associated with kidney disease attributed to type 2 diabetes. The Pima Indians of Arizona have high rates of diabetic nephropathy, which is strongly dependent on genetic determinants; thus, we sought to investigate the role of ELMO1 polym...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Hanson RL,Millis MP,Young NJ,Kobes S,Nelson RG,Knowler WC,DiStefano JK

    更新日期:2010-12-01 00:00:00

  • Enhanced placental cholesterol efflux by fetal HDL in Smith-Lemli-Opitz syndrome.

    abstract::Previous studies from this laboratory have shown that maternal-derived cholesterol can be effluxed from trophoblasts to fetal HDL and plasma. We had the opportunity to study for the first time the ability of HDL and plasma from a fetus with the Smith-Lemli-Opitz syndrome (SLOS) to efflux cholesterol from trophoblasts....

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Jenkins KT,Merkens LS,Tubb MR,Myatt L,Davidson WS,Steiner RD,Woollett LA

    更新日期:2008-06-01 00:00:00

  • A newly generated neuronal cell model of CLN7 disease reveals aberrant lysosome motility and impaired cell survival.

    abstract::Mutations in the CLN7/MFSD8 gene encoding the lysosomal membrane protein CLN7 are causative of CLN7 disease, an inherited neurodegenerative disorder that typically affects children. To gain insight into the pathomechanisms of CLN7 disease, we established an immortalized cell line based on cerebellar (Cb) granule neuro...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: von Kleist L,Ariunbat K,Braren I,Stauber T,Storch S,Danyukova T

    更新日期:2019-02-01 00:00:00

  • Disorders of purine and pyrimidine metabolism.

    abstract::The disorders of purine and pyrimidine metabolism are unusual in their variety of clinical presentations and in the mechanisms by which these presentations result from the fundamental mutations. In the most common of the hyperuricemic metabolic disorders, deficiency of hypoxanthine phosphoribosyl transferase, the fund...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章,评审


    authors: Nyhan WL

    更新日期:2005-09-01 00:00:00

  • The pathogenic role of point mutations affecting the translational initiation codon of mitochondrial genes.

    abstract::The mutation T3308C results in a Met --> Thr change at the highly conserved amino acid position 1 of the mtDNA ND1 gene (M1T). To study its potential pathogenic effect we have carried out a combination of mitochondrial protein synthesis and Northern and Western analyses. Our data demonstrate that M1T mutation does not...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Fernández-Moreno MA,Bornstein B,Campos Y,Arenas J,Garesse R

    更新日期:2000-07-01 00:00:00

  • Outcome and long-term follow-up of 36 patients with tetrahydrobiopterin deficiency.

    abstract::We describe the treatment, the clinical, and biochemical findings and the outcome of 26 patients with 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency and 10 patients with dihydropteridine reductase (DHPR) deficiency. These are the two most common forms of the autosomal-recessively inherited tetrahydrobiopterin ...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Jäggi L,Zurflüh MR,Schuler A,Ponzone A,Porta F,Fiori L,Giovannini M,Santer R,Hoffmann GF,Ibel H,Wendel U,Ballhausen D,Baumgartner MR,Blau N

    更新日期:2008-03-01 00:00:00

  • Association of the acid phosphatase (ACP1) gene with triglyceride levels in obese women.

    abstract::The acid phosphatase (ACP1) locus codes for a low molecular weight protein tyrosine phosphatase (LMPTP) that is found ubiquitously in human tissues. The *A allele of the ACP1 gene is associated with lower total enzymatic activity than the *B and *C alleles. An association between the *A allele and extreme values of bo...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Bottini N,MacMurray J,Peters W,Rostamkhani M,Comings DE

    更新日期:2002-11-01 00:00:00

  • Co-inheritance of a novel deletion of the entire SPINK1 gene with a CFTR missense mutation (L997F) in a family with chronic pancreatitis.

    abstract::Quantitative fluorescent multiplex PCR (QFM-PCR) was established in order to make possible the rapid and efficient mutational analysis of the pancreatic secretory trypsin inhibitor (SPINK1) gene. Using QFM-PCR, a novel heterozygous deletion encompassing the entire SPINK1 gene was identified in one of nine newly recrui...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Masson E,Le Maréchal C,Levy P,Chuzhanova N,Ruszniewski P,Cooper DN,Chen JM,Férec C

    更新日期:2007-09-01 00:00:00

  • Extended [13C]galactose oxidation studies in patients with galactosemia.

    abstract::Since patients with galactose-1-phosphate uridyltransferase (GALT) deficiency have considerable endogenous galactose formation and only limited urinary excretion of galactose metabolites, there must be mechanisms for disposal of the sugar. Otherwise, a steady-state could not be maintained and there would be continuous...

    journal_title:Molecular genetics and metabolism

    pub_type: 临床试验,杂志文章


    authors: Berry GT,Reynolds RA,Yager CT,Segal S

    更新日期:2004-06-01 00:00:00

  • Allelic variations in superoxide dismutase-1 (SOD1) gene and renal and cardiovascular morbidity and mortality in type 2 diabetic subjects.

    abstract:BACKGROUND:Oxidative stress is involved in the pathophysiology of renal and cardiovascular complications of diabetes. Superoxide dismutase (SOD) enzymes play a major role in detoxification of reactive oxygen species and protection against oxidative stress. Associations of SOD1 gene variants with diabetic nephropathy we...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Neves AL,Mohammedi K,Emery N,Roussel R,Fumeron F,Marre M,Velho G

    更新日期:2012-07-01 00:00:00

  • Long-term outcome in methylmalonic aciduria: a series of 30 French patients.

    abstract:OBJECTIVE:To better delineate the natural history of patients with methylmalonic aciduria (MMA). STUDY DESIGN:Thirty patients with vitamin-B12-unresponsive MMA (25 aged 1.5 to 22.0 years (y) at the end of the study and 5 who died during a metabolic crisis) were managed following standardized guidelines and studied ret...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Cosson MA,Benoist JF,Touati G,Déchaux M,Royer N,Grandin L,Jais JP,Boddaert N,Barbier V,Desguerre I,Campeau PM,Rabier D,Valayannopoulos V,Niaudet P,de Lonlay P

    更新日期:2009-07-01 00:00:00

  • Novel missense mutations in PNPLA2 causing late onset and clinical heterogeneity of neutral lipid storage disease with myopathy in three siblings.

    abstract::Neutral lipid storage disease with myopathy (NLSD-M) is a rare autosomal recessive disorder characterised by an abnormal accumulation of triacylglycerol into cytoplasmic lipid droplets (LDs). NLSD-M patients are mainly affected by progressive myopathy, cardiomyopathy and hepatomegaly. Mutations in the PNPLA2 gene caus...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Missaglia S,Tasca E,Angelini C,Moro L,Tavian D

    更新日期:2015-06-01 00:00:00

  • A spectrum of molecular variation in a cohort of Italian families with trimethylaminuria: identification of three novel mutations of the FM03 gene.

    abstract::Fish-odor syndrome or trimethylaminuria, is a rare inborn error of metabolism inherited in an autosomal recessive fashion, involving the dysfunction of hepatic enzyme flavin-containing monooxygenase 3 (FMO3) that converts fishy-smelling trimethylamine (TMA) into odorless trimethylamine-N-oxide (TMAO). This confers, to...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Teresa E,Lonardo F,Fiumara A,Lombardi C,Russo P,Zuppi C,Scarano G,Musumeci S,Gianfrancesco F

    更新日期:2006-06-01 00:00:00

  • Transfection screening for defects in the PCCA and PCCB genes encoding propionyl-CoA carboxylase subunits.

    abstract::Propionic acidemia can result from mutations in the PCCA or PCCB genes encoding the alpha and beta subunits, respectively, of propionyl-CoA carboxylase. We have developed a method based on complementation of the enzyme defect using a lipid-mediated transient transfection of the normal human PCCA or PCCB cDNA into prim...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Rodriguez-Pombo P,Pérez-Cerdá C,Desviat LR,Pérez B,Ugarte M,Rodríguez-Pombo P

    更新日期:2002-03-01 00:00:00

  • Exclusion of SOX9 as the testis determining factor in Ellobius lutescens: evidence for another testis determining gene besides SRY and SOX9.

    abstract::In mammals the initiation of testis determination usually depends on the Y-chromosomal gene SRY. A few species, however, escape from this rule with a testis determination that is independent of SRY. The mole vole Ellobius lutescens is one of these species. It is not known how testis determination is initiated in this ...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Baumstark A,Akhverdyan M,Schulze A,Reisert I,Vogel W,Just W

    更新日期:2001-01-01 00:00:00

  • Successful combined liver/kidney transplantation from a donor with Pompe disease.

    abstract::Pompe disease results from inherited deficiency of the enzyme acid alpha-glucosidase resulting in lysosomal accumulation of glycogen primarily in skeletal muscle. Reported is the first case in which a donor with late onset Pompe disease (LOPD) was successfully used for deceased donor liver and kidney transplantation. ...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章,评审


    authors: Halldorson J,Kazi Z,Mekeel K,Kuo A,Hassanein T,Loomba R,Austin S,Valasek MA,Kishnani P,Hemming AW

    更新日期:2015-08-01 00:00:00

  • The designer aminoglycoside NB84 significantly reduces glycosaminoglycan accumulation associated with MPS I-H in the Idua-W392X mouse.

    abstract::Suppression therapy utilizes compounds that suppress translation termination at in-frame premature termination codons (PTCs) to restore full-length, functional protein. This approach may provide a treatment for diseases caused by nonsense mutations such as mucopolysaccharidosis type I-Hurler (MPS I-H). MPS I-H is a ly...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Wang D,Belakhov V,Kandasamy J,Baasov T,Li SC,Li YT,Bedwell DM,Keeling KM

    更新日期:2012-01-01 00:00:00

  • Neurocognitive functioning in adults with phenylketonuria: Report of a 10-year follow-up.

    abstract:BACKGROUND:The long-term prognosis of early treated phenylketonuria (PKU) is still under discussion. Aim of this controlled long-term study was to assess the neurological and neuropsychological outcome in adult patients with early-treated PKU. METHODS:We investigated 35 patients with early-treated classical PKU aged 2...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Feldmann R,Osterloh J,Onon S,Fromm J,Rutsch F,Weglage J

    更新日期:2019-03-01 00:00:00

  • The functions of RPS19 and their relationship to Diamond-Blackfan anemia: a review.

    abstract::The relatively new study of ribosomal proteins has allowed for greater understanding of protein synthesis; however the connection between ribosomal proteins' roles and that of disease pathophysiology has not yet been established. RPS19 is a ribosomal protein linked to Diamond-Blackfan anemia whose functions have begun...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章,评审


    authors: Morimoto K,Lin S,Sakamoto K

    更新日期:2007-04-01 00:00:00

  • Tetrahydrobiopterin responsiveness: results of the BH4 loading test in 31 Spanish PKU patients and correlation with their genotype.

    abstract::Tetrahydrobiopterin (BH4) responsiveness in patients with mutations in the phenylalanine hydroxylase (PAH) gene is a recently recognized subtype of hyperphenylalaninemia characterized by a positive BH4 loading test. According to recent estimates, this phenotype may be quite common, suggesting that a large group of ind...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Desviat LR,Pérez B,Bèlanger-Quintana A,Castro M,Aguado C,Sánchez A,García MJ,Martínez-Pardo M,Ugarte M

    更新日期:2004-09-01 00:00:00

  • Uncovering microdeletions in patients with severe Glut-1 deficiency syndrome using SNP oligonucleotide microarray analysis.

    abstract::Glut-1 facilitates the diffusion of glucose across the blood-brain barrier and is responsible for glucose entry into the brain. Impaired glucose transport across the blood-brain barrier results in Glut-1 deficiency syndrome (Glut-1 DS, OMIM 606777), characterized in its most severe form by infantile seizures, developm...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Levy B,Wang D,Ullner PM,Engelstad K,Yang H,Nahum O,Chung WK,De Vivo DC

    更新日期:2010-06-01 00:00:00

  • Homozygous variegate porphyria in South Africa: genotypic analysis in two cases.

    abstract::Variegate porphyria is an autosomal dominant disorder of heme metabolism which results from decreased activity of the enzyme protoporphyrinogen oxidase. Clinically, the disease manifests postpubertally and is characterized by photocutaneous sensitivity and/or acute neurovisceral crises. However, in homozygous variegat...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Corrigall AV,Hift RJ,Davids LM,Hancock V,Meissner D,Kirsch RE,Meissner PN

    更新日期:2000-04-01 00:00:00

  • Late diagnosis of maternal PKU in a family segregating an arylsulfatase [corrected] E mutation causing symmetrical chondrodysplasia punctata.

    abstract::Mutations in the arylsulfatase E gene, located on the X chromosome, have been shown to cause chondrodysplasia punctata (CDP). A substitution of arginine with serine at amino acid 12 (R12S) was identified in a patient with typical features of mild symmetrical CDP including mild mental retardation. The proband was insti...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Dahl HH,Osborn AH,Hutchison WM,Thorburn DR,Sheffield LJ

    更新日期:1999-12-01 00:00:00

  • Low plasma total cholesterol in patients with Huntington's disease and first-degree relatives.

    abstract::Recent studies indicate altered cholesterol homeostasis in Huntington's disease (HD) after it was found that cultured human and mice cells expressing mutant huntingtin show reduced mRNA of cholesterol biosynthetic enzymes. Plasma total cholesterol (TC) levels have been connected to degenerative disorders, but data for...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Markianos M,Panas M,Kalfakis N,Vassilopoulos D

    更新日期:2008-03-01 00:00:00

  • Polygenic association with total homocysteine in the post-folic acid fortification era: the CARDIA study.

    abstract::Elevated plasma concentration of total homocysteine (tHcy) has been linked with many diseases. tHcy is associated with a variety of factors, including polymorphisms in genes involved in homocysteine metabolism. It is not clear whether US-mandated fortification of grain products with folic acid has affected the associa...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Tsai MY,Loria CM,Cao J,Kim Y,Siscovick DS,Schreiner PJ,Hanson NQ

    更新日期:2009-09-01 00:00:00

  • Clinical presentation and outcome in a series of 32 patients with 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency.

    abstract::2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency, also known as beta-ketothiolase deficiency, is an inborn error of ketone body utilization and isoleucine catabolism. It is caused by mutations in the ACAT1 gene and may present with metabolic ketoacidosis. In order to obtain a more comprehensive view on this di...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Grünert SC,Schmitt RN,Schlatter SM,Gemperle-Britschgi C,Balcı MC,Berg V,Çoker M,Das AM,Demirkol M,Derks TGJ,Gökçay G,Uçar SK,Konstantopoulou V,Christoph Korenke G,Lotz-Havla AS,Schlune A,Staufner C,Tran C,Visser G,S

    更新日期:2017-09-01 00:00:00

  • Treatment reduces or stabilizes brain imaging abnormalities in patients with MPS I and II.

    abstract:BACKGROUND:The mucopolysaccharidoses (MPSs) are a family of lysosomal storage disorders caused by impaired glycosaminoglycan degradation. Characteristic brain imaging abnormalities are seen in MPS patients. This study aims to determine the effects of hematopoietic stem cell transplantation (HSCT) and/or intravenous enz...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Wang RY,Cambray-Forker EJ,Ohanian K,Karlin DS,Covault KK,Schwartz PH,Abdenur JE

    更新日期:2009-12-01 00:00:00

  • Phenotypic heterogeneity in the presentation of D-2-hydroxyglutaric aciduria in monozygotic twins.

    abstract::D-2-hydroxyglutaric aciduria (D-2-HGA) is a very rare autosomal recessive metabolic disorder that has recently been associated with mutations in the D-2-hydroxyglutarate dehydrogenase gene. The biochemical phenotype of D-2-HGA is defined by the accumulation of abnormal amounts of D-2-hydroxyglutarate in cerebrospinal ...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Misra VK,Struys EA,O'brien W,Salomons GS,Glover T,Jakobs C,Innis JW

    更新日期:2005-09-01 00:00:00

  • CFTR mutation analysis and haplotype associations in CF patients.

    abstract::Most newborn screening (NBS) laboratories use second-tier molecular tests for cystic fibrosis (CF) using dried blood spots (DBS). The Centers for Disease Control and Prevention's NBS Quality Assurance Program offers proficiency testing (PT) in DBS for CF transmembrane conductance regulator (CFTR) gene mutation detecti...

    journal_title:Molecular genetics and metabolism

    pub_type: 杂志文章


    authors: Cordovado SK,Hendrix M,Greene CN,Mochal S,Earley MC,Farrell PM,Kharrazi M,Hannon WH,Mueller PW

    更新日期:2012-02-01 00:00:00