当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > A genetic modifier suggests that endurance exercise exacerbates Huntington's disease.

A genetic modifier suggests that endurance exercise exacerbates Huntington's disease.

Abstract：

:Polyglutamine expansions in the huntingtin gene cause Huntington's disease (HD). Huntingtin is ubiquitously expressed, leading to pathological alterations also in peripheral organs. Variations in the length of the polyglutamine tract explain up to 70% of the age-at-onset variance, with the rest of the variance attributed to genetic and environmental modifiers. To identify novel disease modifiers, we performed an unbiased mutagenesis screen on an HD mouse model, identifying a mutation in the skeletal muscle voltage-gated sodium channel (Scn4a, termed 'draggen' mutation) as a novel disease enhancer. Double mutant mice (HD; Scn4aDgn/+) had decreased survival, weight loss and muscle atrophy. Expression patterns show that the main tissue affected is skeletal muscle. Intriguingly, muscles from HD; Scn4aDgn/+ mice showed adaptive changes similar to those found in endurance exercise, including AMPK activation, fibre type switching and upregulation of mitochondrial biogenesis. Therefore, we evaluated the effects of endurance training on HD mice. Crucially, this training regime also led to detrimental effects on HD mice. Overall, these results reveal a novel role for skeletal muscle in modulating systemic HD pathogenesis, suggesting that some forms of physical exercise could be deleterious in neurodegeneration.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Corrochano S,Blanco G,Williams D,Wettstein J,Simon M,Kumar S,Moir L,Agnew T,Stewart M,Landman A,Kotiadis VN,Duchen MR,Wackerhage H,Rubinsztein DC,Brown SDM,Acevedo-Arozena A

doi

10.1093/hmg/ddy077

subject

Has Abstract

pub_date

2018-05-15 00:00:00

pages

1723-1731

issue

10

eissn

0964-6906

issn

1460-2083

pii

4917553

journal_volume

27

pub_type

杂志文章

相关文献

HUMAN MOLECULAR GENETICS文献大全
  • IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome.

    abstract：:Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy with multisystem involvement. So far, 18 BBS genes have been identified and the majority of them are essential for the function of BBSome, a protein complex involved in transporting membrane proteins into and from cilia. Yet defects in the identified gen...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu044

    authors： Aldahmesh MA,Li Y,Alhashem A,Anazi S,Alkuraya H,Hashem M,Awaji AA,Sogaty S,Alkharashi A,Alzahrani S,Al Hazzaa SA,Xiong Y,Kong S,Sun Z,Alkuraya FS

    更新日期：2014-06-15 00:00:00

  • Functional evaluation of genetic variation in complex human traits.

    abstract：:Genome-wide association studies and, more recently, next-generation sequencing studies have accelerated the investigation of complex human traits by providing a wealth of association data linking genetic variants to diseases and other phenotypic traits. These data promise to transform our understanding of the molecula...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/dds363

    authors： Peters DT,Musunuru K

    更新日期：2012-10-15 00:00:00

  • Fragile sites and human disease.

    abstract：:A relationship between fragile sites, specific genomic regions visible as gaps or breaks on cultivated chromosomes, and human disease has been proposed many years ago. Evidence for a role of the ubiquitously expressed common fragile sites characterized by peculiar genome architecture in cancer has been accumulated ove...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/ddm136

    authors： Debacker K,Kooy RF

    更新日期：2007-10-15 00:00:00

  • Paternal monoallelic expression of PEG3 in the human placenta.

    abstract：:Genomic imprinting is the phenomenon whereby mono-allelic expression of certain genes occurs depending on their parental origin. The observation that imprinting only occurs in placental mammals has led to the suggestion that it may play a role in this form of reproduction. In the present study we have investigated the...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/10.10.1093

    authors： Hiby SE,Lough M,Keverne EB,Surani MA,Loke YW,King A

    更新日期：2001-05-01 00:00:00

  • Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25.

    abstract：:Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu511

    authors： Litchfield K,Sultana R,Renwick A,Dudakia D,Seal S,Ramsay E,Powell S,Elliott A,Warren-Perry M,Eeles R,Peto J,Kote-Jarai Z,Muir K,Nsengimana J,UKTCC.,Stratton MR,Easton DF,Bishop DT,Huddart RA,Rahman N,Turnbull C,

    更新日期：2015-02-15 00:00:00

  • Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability.

    abstract：:The integrity and dynamic properties of the microtubule cytoskeleton are indispensable for the development of the mammalian brain. Consequently, mutations in the genes that encode the structural component (the α/β-tubulin heterodimer) can give rise to severe, sporadic neurodevelopmental disorders. These are commonly r...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw383

    authors： Breuss MW,Nguyen T,Srivatsan A,Leca I,Tian G,Fritz T,Hansen AH,Musaev D,McEvoy-Venneri J,James KN,Rosti RO,Scott E,Tan U,Kolodner RD,Cowan NJ,Keays DA,Gleeson JG

    更新日期：2017-01-15 00:00:00

  • Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability.

    abstract：:Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA,...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv286

    authors： Heidari A,Tongsook C,Najafipour R,Musante L,Vasli N,Garshasbi M,Hu H,Mittal K,McNaughton AJ,Sritharan K,Hudson M,Stehr H,Talebi S,Moradi M,Darvish H,Arshad Rafiq M,Mozhdehipanah H,Rashidinejad A,Samiei S,Ghadami M,

    更新日期：2015-10-15 00:00:00

  • Intermediate filament protein accumulation in motor neurons derived from giant axonal neuropathy iPSCs rescued by restoration of gigaxonin.

    abstract：:Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene resulting in a loss of a ubiquitously expressed protein, gigaxonin. Gene replacement therapy is a promising strategy for treatment of the disease; however, the effectiveness and safety of gi...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu556

    authors： Johnson-Kerner BL,Ahmad FS,Diaz AG,Greene JP,Gray SJ,Samulski RJ,Chung WK,Van Coster R,Maertens P,Noggle SA,Henderson CE,Wichterle H

    更新日期：2015-03-01 00:00:00

  • Histone acetylation dependent allelic expression imbalance of BAPX1 in patients with the oculo-auriculo-vertebral spectrum.

    abstract：:The oculo-auriculo-vertebral spectrum (OAVS) (OMIM % 164210) is a common developmental disorder characterized by hemifacial microsomia, epibulbar tumours, ear malformation and vertebral anomalies. Although rare familial cases suggest that OAVS has a genetic basis, no genetic defect has been identified so far. In a pat...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddi474

    authors： Fischer S,Lüdecke HJ,Wieczorek D,Böhringer S,Gillessen-Kaesbach G,Horsthemke B

    更新日期：2006-02-15 00:00:00

  • Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty.

    abstract：:Little is known about genes regulating male puberty. Further, while many identified pubertal timing variants associate with age at menarche, a late manifestation of puberty, and body mass, little is known about these variants' relationship to pubertal initiation or tempo. To address these questions, we performed genom...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,meta分析

    doi：10.1093/hmg/ddu150

    authors： Cousminer DL,Stergiakouli E,Berry DJ,Ang W,Groen-Blokhuis MM,Körner A,Siitonen N,Ntalla I,Marinelli M,Perry JR,Kettunen J,Jansen R,Surakka I,Timpson NJ,Ring S,Mcmahon G,Power C,Wang C,Kähönen M,Viikari J,Lehtimäki

    更新日期：2014-08-15 00:00:00

  • The role of the mitochondrial ribosome in human disease: searching for mutations in 12S mitochondrial rRNA with high disruptive potential.

    abstract：:Mutations of mitochondrial DNA are linked to many human diseases. Despite the identification of a large number of variants in the mitochondrially encoded rRNA (mt-rRNA) genes, the evidence supporting their pathogenicity is, at best, circumstantial. Establishing the pathogenicity of these variations is of major diagnos...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt490

    authors： Smith PM,Elson JL,Greaves LC,Wortmann SB,Rodenburg RJ,Lightowlers RN,Chrzanowska-Lightowlers ZM,Taylor RW,Vila-Sanjurjo A

    更新日期：2014-02-15 00:00:00

  • Reduced cell proliferation and increased apoptosis are significant pathological mechanisms in a murine model of mild pseudoachondroplasia resulting from a mutation in the C-terminal domain of COMP.

    abstract：:Pseudoachondroplasia (PSACH) is one of the more common skeletal dysplasias and results from mutations in cartilage oligomeric matrix protein (COMP). Most COMP mutations identified to date cluster in the TSP3 repeat region of COMP and the mutant protein is retained in the rough endoplasmic reticulum (rER) of chondrocyt...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm155

    authors： Piróg-Garcia KA,Meadows RS,Knowles L,Heinegård D,Thornton DJ,Kadler KE,Boot-Handford RP,Briggs MD

    更新日期：2007-09-01 00:00:00

  • Genomic, genetic and functional dissection of bitter taste responses to artificial sweeteners.

    abstract：:Bitter taste perception is initiated by TAS2R receptors, which respond to agonists by triggering depolarization of taste bud cells. Mutations in TAS2Rs are known to affect taste phenotypes by altering receptor function. Evidence that TAS2Rs overlap in ligand specificity suggests that they may also contribute joint eff...

    journal_title：Human molecular genetics

    pub_type： 临床试验,杂志文章

    doi：10.1093/hmg/ddr252

    authors： Roudnitzky N,Bufe B,Thalmann S,Kuhn C,Gunn HC,Xing C,Crider BP,Behrens M,Meyerhof W,Wooding SP

    更新日期：2011-09-01 00:00:00

  • Biologically active molecules that reduce polyglutamine aggregation and toxicity.

    abstract：:Polyglutamine expansion in certain proteins causes neurodegeneration in inherited disorders such as Huntington disease and X-linked spinobulbar muscular atrophy. Polyglutamine tracts promote protein aggregation in vitro and in vivo with a strict length-dependence that strongly implicates alternative protein folding an...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddl135

    authors： Desai UA,Pallos J,Ma AA,Stockwell BR,Thompson LM,Marsh JL,Diamond MI

    更新日期：2006-07-01 00:00:00

  • The evolutionary distribution and structural organization of the homeobox-containing repeat D4Z4 indicates a functional role for the ancestral copy in the FSHD region.

    abstract：:Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disease that has been linked to deletions within a tandem array of 3.2 kb repeats adjacent to the telomere of 4q. These repeats are also present in other locations in the human genome, including the short arms of all the acrocentric c...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/5.10.1567

    authors： Winokur ST,Bengtsson U,Vargas JC,Wasmuth JJ,Altherr MR,Weiffenbach B,Jacobsen SJ

    更新日期：1996-10-01 00:00:00

  • Delivery of recombinant follistatin lessens disease severity in a mouse model of spinal muscular atrophy.

    abstract：:Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. SMA is caused by loss of functional survival motor neuron 1 (SMN1), resulting in death of spinal motor neurons. Current therapeutic research focuses on modulating the expression of a partially functioning copy gene, SMN2, which is reta...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddn426

    authors： Rose FF Jr,Mattis VB,Rindt H,Lorson CL

    更新日期：2009-03-15 00:00:00

  • Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly.

    abstract：:We report two siblings with infantile onset seizures, severe developmental delay and spastic paraplegia, in whom whole-genome sequencing revealed compound heterozygous mutations in the AP4S1 gene, encoding the σ subunit of the adaptor protein complex 4 (AP-4). The effect of the predicted loss-of-function variants (p.G...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu740

    authors： Hardies K,May P,Djémié T,Tarta-Arsene O,Deconinck T,Craiu D,AR working group of the EuroEPINOMICS RES Consortium.,Helbig I,Suls A,Balling R,Weckhuysen S,De Jonghe P,Hirst J

    更新日期：2015-04-15 00:00:00

  • Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation.

    abstract：:Genetic analysis of mouse mutants has demonstrated the importance of the homeobox genes Rpx, Lhx3 and Pit1 for anterior pituitary gland development. Pit1 mutations have also been identified in several human families with multiple pituitary hormone deficiencies. To identify additional homeobox regulators of pituitary d...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/6.3.457

    authors： Gage PJ,Camper SA

    更新日期：1997-03-01 00:00:00

  • Single cell ATAC-Seq reveals cell type-specific transcriptional regulation and unique chromatin accessibility in human spermatogenesis.

    abstract：:During human spermatogenesis, germ cells undergo dynamic changes in chromatin organization/re-packaging and in transcriptomes. In order to better understand the underlying mechanism(s), scATAC-Seq of 5376 testicular cells from 3 normal men were performed. Data were analyzed in parallel with the scRNA-Seq data of human...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddab006

    authors： Wu X,Lu M,Yun D,Gao S,Chen S,Hu L,Wu Y,Wang X,Duan E,Cheng CY,Sun F

    更新日期：2021-01-12 00:00:00

  • Discovery and genetic localization of Down syndrome cerebellar phenotypes using the Ts65Dn mouse.

    abstract：:Down syndrome (DS) is the most common genetic cause of mental retardation and affects many aspects of brain development. DS individuals exhibit an overall reduction in brain size with a disproportionately greater reduction in cerebellar volume. The Ts65Dn mouse is segmentally trisomic for the distal 12-15 Mb of mouse ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.2.195

    authors： Baxter LL,Moran TH,Richtsmeier JT,Troncoso J,Reeves RH

    更新日期：2000-01-22 00:00:00

  • Calpain-1 ablation partially rescues disease-associated hallmarks in models of Machado-Joseph disease.

    abstract：:Proteolytic fragmentation of polyglutamine-expanded ataxin-3 is a concomitant and modifier of the molecular pathogenesis of Machado-Joseph disease (MJD), the most common autosomal dominant cerebellar ataxia. Calpains, a group of calcium-dependent cysteine proteases, are important mediators of ataxin-3 cleavage and imp...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddaa010

    authors： Weber JJ,Haas E,Maringer Y,Hauser S,Casadei NLP,Chishti AH,Riess O,Hübener-Schmid J

    更新日期：2020-04-15 00:00:00

  • Mutant superoxide dismutase 1 (SOD1), a cause of amyotrophic lateral sclerosis, disrupts the recruitment of SMN, the spinal muscular atrophy protein to nuclear Cajal bodies.

    abstract：:Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are among the most common motor neuron diseases to afflict the human population. A deficiency of the survival of motor neuron (SMN) protein causes SMA and is also reported to be an exacerbating factor in the development of ALS. However, pathways lin...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds174

    authors： Kariya S,Re DB,Jacquier A,Nelson K,Przedborski S,Monani UR

    更新日期：2012-08-01 00:00:00

  • Copper-dependent trafficking of Wilson disease mutant ATP7B proteins.

    abstract：:We have previously developed a functional assay in yeast for the copper transporter, ATP7B, defective in Wilson disease (WND). Analysis of WND variant ATP7B proteins revealed that several were able to completely, or nearly completely, complement a mutant yeast strain in which the ATP7B ortholog CCC2 was disrupted, ind...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.13.1927

    authors： Forbes JR,Cox DW

    更新日期：2000-08-12 00:00:00

  • Dysregulation of 4q35- and muscle-specific genes in fetuses with a short D4Z4 array linked to facio-scapulo-humeral dystrophy.

    abstract：:Facio-scapulo-humeral dystrophy (FSHD) results from deletions in the subtelomeric macrosatellite D4Z4 array on the 4q35 region. Upregulation of the DUX4 retrogene from the last D4Z4 repeated unit is thought to underlie FSHD pathophysiology. However, no one knows what triggers muscle defect and when alteration arises. ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt272

    authors： Broucqsault N,Morere J,Gaillard MC,Dumonceaux J,Torrents J,Salort-Campana E,Maues De Paula A,Bartoli M,Fernandez C,Chesnais AL,Ferreboeuf M,Sarda L,Dufour H,Desnuelle C,Attarian S,Levy N,Nguyen K,Magdinier F,Roche S

    更新日期：2013-10-15 00:00:00

  • Multifaceted Hoxa13 function in urogenital development underlies the Hand-Foot-Genital Syndrome.

    abstract：:Hand-Foot-Genital syndrome is a rare condition caused by mutations in the HOXA13 gene and characterized by limb malformations and urogenital defects. While the role of Hoxa13 in limb development has been extensively studied, its function during the development of the urogenital system remains elusive mostly due to the...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddz013

    authors： Roux M,Bouchard M,Kmita M

    更新日期：2019-05-15 00:00:00

  • Integrative genome and transcriptome analyses reveal two distinct types of ring chromosome in soft tissue sarcomas.

    abstract：:Gene amplification is a common phenomenon in malignant neoplasms of all types. One mechanism behind increased gene copy number is the formation of ring chromosomes. Such structures are mitotically unstable and during tumor progression they accumulate material from many different parts of the genome. Hence, their conte...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt479

    authors： Nord KH,Macchia G,Tayebwa J,Nilsson J,Vult von Steyern F,Brosjö O,Mandahl N,Mertens F

    更新日期：2014-02-15 00:00:00

  • Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy.

    abstract：:Spinal muscular atrophy (SMA) is a common pediatric neuromuscular disorder caused by insufficient levels of the survival of motor neuron (SMN) protein. Studies involving SMA patients and animal models expressing the human SMN2 gene have yielded relatively little information about the earliest cellular consequences of ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddn156

    authors： Kariya S,Park GH,Maeno-Hikichi Y,Leykekhman O,Lutz C,Arkovitz MS,Landmesser LT,Monani UR

    更新日期：2008-08-15 00:00:00

  • Nuclear receptor NR2E3 gene mutations distort human retinal laminar architecture and cause an unusual degeneration.

    abstract：:Mutations in the nuclear receptor gene, NR2E3, cause a disorder of human retinal photoreceptor development characterized by hyperfunction and excess of the minority S (short wavelength or blue) cone photoreceptor type, but near absence of function of the majority rod receptor. NR2E3 disease can also progress to blindn...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddh198

    authors： Jacobson SG,Sumaroka A,Aleman TS,Cideciyan AV,Schwartz SB,Roman AJ,McInnes RR,Sheffield VC,Stone EM,Swaroop A,Wright AF

    更新日期：2004-09-01 00:00:00

  • Deletion of the miR-379/miR-410 gene cluster at the imprinted Dlk1-Dio3 locus enhances anxiety-related behaviour.

    abstract：:The brain-specific miR-379/miR-410 gene cluster at the imprinted Dlk1-Dio3 domain is implicated in several aspects of brain development and function, particularly in fine-tuning the dendritic outgrowth and spine remodelling of hippocampal neurons. Whether it might influence behaviour and memory-related processes has n...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv510

    authors： Marty V,Labialle S,Bortolin-Cavaillé ML,Ferreira De Medeiros G,Moisan MP,Florian C,Cavaillé J

    更新日期：2016-02-15 00:00:00

  • TOPORS, implicated in retinal degeneration, is a cilia-centrosomal protein.

    abstract：:We recently reported that mutations in the widely expressed nuclear protein TOPORS (topoisomerase I-binding arginine/serine rich) are associated with autosomal dominant retinal degeneration. However, the precise localization and a functional role of TOPORS in the retina remain unknown. Here, we demonstrate that TOPORS...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddq543

    authors： Chakarova CF,Khanna H,Shah AZ,Patil SB,Sedmak T,Murga-Zamalloa CA,Papaioannou MG,Nagel-Wolfrum K,Lopez I,Munro P,Cheetham M,Koenekoop RK,Rios RM,Matter K,Wolfrum U,Swaroop A,Bhattacharya SS

    更新日期：2011-03-01 00:00:00