当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice.

Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice.

Abstract：

:Peroxisome proliferator-activated receptors (PPARs) are ligand-mediated transcription factors, which control both lipid and energy metabolism and inflammation pathways. PPARγ agonists are effective in the treatment of metabolic diseases and, more recently, neurodegenerative diseases, in which they show promising neuroprotective effects. We studied the effects of the pan-PPAR agonist bezafibrate on tau pathology, inflammation, lipid metabolism and behavior in transgenic mice with the P301S human tau mutation, which causes familial frontotemporal lobar degeneration. Bezafibrate treatment significantly decreased tau hyperphosphorylation using AT8 staining and the number of MC1-positive neurons. Bezafibrate treatment also diminished microglial activation and expression of both inducible nitric oxide synthase and cyclooxygenase 2. Additionally, the drug differentially affected the brain and brown fat lipidome of control and P301S mice, preventing lipid vacuoles in brown fat. These effects were associated with behavioral improvement, as evidenced by reduced hyperactivity and disinhibition in the P301S mice. Bezafibrate therefore exerts neuroprotective effects in a mouse model of tauopathy, as shown by decreased tau pathology and behavioral improvement. Since bezafibrate was given to the mice before tau pathology had developed, our data suggest that bezafibrate exerts a preventive effect on both tau pathology and its behavioral consequences. Bezafibrate is therefore a promising agent for the treatment of neurodegenerative diseases associated with tau pathology.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Dumont M,Stack C,Elipenahli C,Jainuddin S,Gerges M,Starkova N,Calingasan NY,Yang L,Tampellini D,Starkov AA,Chan RB,Di Paolo G,Pujol A,Beal MF

doi

10.1093/hmg/dds355

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

5091-105

issue

23

eissn

0964-6906

issn

1460-2083

pii

dds355

journal_volume

21

pub_type

杂志文章

相关文献

HUMAN MOLECULAR GENETICS文献大全
  • Assignment of an Usher syndrome type III (USH3) gene to chromosome 3q.

    abstract：:Usher syndrome (USH) refers to genetically and clinically heterogeneous autosomal recessive disorders with combined visual and hearing loss. Type I (USH1) is characterized by a congenital, severe to profound hearing loss and absent vestibular function; in type II (USH2) the hearing loss is congenital and moderate to s...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/4.1.93

    authors： Sankila EM,Pakarinen L,Kääriäinen H,Aittomäki K,Karjalainen S,Sistonen P,de la Chapelle A

    更新日期：1995-01-01 00:00:00

  • Preimplantation prevention of X-linked disease: reliable and rapid sex determination of single human cells by restriction analysis of simultaneously amplified ZFX and ZFY sequences.

    abstract：:In vitro fertilization (IVF), blastomere biopsy of the 6-8 cell embryo, and single cell DNA diagnosis allows couples at risk of transmitting an X-linked or autosomal disease to start a pregnancy knowing their child will not be affected. We present a quick and reliable nested PCR strategy for sex determination at the s...

    journal_title：Human molecular genetics

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：10.1093/hmg/2.8.1187

    authors： Chong SS,Kristjansson K,Cota J,Handyside AH,Hughes MR

    更新日期：1993-08-01 00:00:00

  • Mutant HSPB8 causes motor neuron-specific neurite degeneration.

    abstract：:Missense mutations (K141N and K141E) in the alpha-crystallin domain of the small heat shock protein HSPB8 (HSP22) cause distal hereditary motor neuropathy (distal HMN) or Charcot-Marie-Tooth neuropathy type 2L (CMT2L). The mechanism through which mutant HSPB8 leads to a specific motor neuron disease phenotype is curre...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddq234

    authors： Irobi J,Almeida-Souza L,Asselbergh B,De Winter V,Goethals S,Dierick I,Krishnan J,Timmermans JP,Robberecht W,De Jonghe P,Van Den Bosch L,Janssens S,Timmerman V

    更新日期：2010-08-15 00:00:00

  • COPI transport complexes bind to specific RNAs in neuronal cells.

    abstract：:Our fundamental understanding of how several thousand diverse RNAs are recognized in the soma, sorted, packaged, transported and localized within the cell is fragmentary. The COPa and COPb proteins of the coatomer protein I (COPI) vesicle complex were reported to interact with specific RNAs and represent a candidate R...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds480

    authors： Todd AG,Lin H,Ebert AD,Liu Y,Androphy EJ

    更新日期：2013-02-15 00:00:00

  • p19-INK4d inhibits neuroblastoma cell growth, induces differentiation and is hypermethylated and downregulated in MYCN-amplified neuroblastomas.

    abstract：:Uncontrolled cell cycle entry, resulting from deregulated CDK-RB1-E2F pathway activity, is a crucial determinant of neuroblastoma cell malignancy. Here we identify neuroblastoma-suppressive functions of the p19-INK4d CDK inhibitor and uncover mechanisms of its repression in high-risk neuroblastomas. Reduced p19-INK4d ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu406

    authors： Dreidax D,Bannert S,Henrich KO,Schröder C,Bender S,Oakes CC,Lindner S,Schulte JH,Duffy D,Schwarzl T,Saadati M,Ehemann V,Benner A,Pfister S,Fischer M,Westermann F

    更新日期：2014-12-20 00:00:00

  • Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy.

    abstract：:The striated muscle sarcomeres are highly organized structures composed of actin (thin) and myosin (thick) filaments that slide past each other during contraction. The integrity of sarcomeres is controlled by a set of structural proteins, among which are titin, a giant molecule that contains several immunoglobulin (Ig...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/8.7.1329

    authors： Salmikangas P,Mykkänen OM,Grönholm M,Heiska L,Kere J,Carpén O

    更新日期：1999-07-01 00:00:00

  • Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene: correlation between sulfate transport activity and chondrodysplasia phenotype.

    abstract：:The diastrophic dysplasia sulfate transporter (DTDST) gene encodes a transmembrane protein that transports sulfate into chondrocytes to maintain adequate sulfation of proteoglycans. Mutations in this gene are responsible for four recessively inherited chondrodysplasias that include diastrophic dysplasia, multiple epip...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/10.14.1485

    authors： Karniski LP

    更新日期：2001-07-01 00:00:00

  • Differences in assembly or stability of complex I and other mitochondrial OXPHOS complexes in inherited complex I deficiency.

    abstract：:NADH-ubiquinone oxidoreductase (complex I) deficiency is amongst the most encountered defects of the mitochondrial oxidative phosphorylation (OXPHOS) system and is associated with a wide variety of clinical signs and symptoms. Mutations in complex I nuclear structural genes are the most common cause of isolated comple...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddh071

    authors： Ugalde C,Janssen RJ,van den Heuvel LP,Smeitink JA,Nijtmans LG

    更新日期：2004-03-15 00:00:00

  • Initiation of the breakage-fusion-bridge mechanism through common fragile site activation in human breast cancer cells: the model of PIP gene duplication from a break at FRA7I.

    abstract：:Gene amplification plays a critical role in tumor progression. Hence, understanding the factors triggering this process in human cancers is an important concern. Unfortunately, the structures formed at early stages are usually unavailable for study, hampering the identification of the initiating events in tumors. Here...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/11.23.2887

    authors： Ciullo M,Debily MA,Rozier L,Autiero M,Billault A,Mayau V,El Marhomy S,Guardiola J,Bernheim A,Coullin P,Piatier-Tonneau D,Debatisse M

    更新日期：2002-11-01 00:00:00

  • Neuregulin 1 type III improves peripheral nerve myelination in a mouse model of congenital hypomyelinating neuropathy.

    abstract：:Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from the axonal protein neuregulin 1 (NRG1) type III regulate Schwann cell fate and myelination. Here we ask if modulating NRG1 type III le...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy420

    authors： Belin S,Ornaghi F,Shackleford G,Wang J,Scapin C,Lopez-Anido C,Silvestri N,Robertson N,Williamson C,Ishii A,Taveggia C,Svaren J,Bansal R,Schwab MH,Nave K,Fratta P,D'Antonio M,Poitelon Y,Feltri ML,Wrabetz L

    更新日期：2019-04-15 00:00:00

  • DNA methylation profiling in human Huntington's disease brain.

    abstract：:Despite extensive progress in Huntington's disease (HD) research, very little is known about the association of epigenetic variation and HD pathogenesis in human brain tissues. Moreover, its contribution to the tissue-specific transcriptional regulation of the huntingtin gene (HTT), in which HTT expression levels are ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw076

    authors： De Souza RA,Islam SA,McEwen LM,Mathelier A,Hill A,Mah SM,Wasserman WW,Kobor MS,Leavitt BR

    更新日期：2016-05-15 00:00:00

  • Endoplasmic reticulum stress-induced caspase-4 activation mediates apoptosis and neurodegeneration in INCL.

    abstract：:Infantile neuronal ceroid lipofuscinosis (INCL), a neurodegenerative storage disorder of childhood, is caused by mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 cleaves thioester linkages in S-acylated (palmitoylated) proteins and its mutation causes abnormal intracellular accumulation of fatty-acy...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddl105

    authors： Kim SJ,Zhang Z,Hitomi E,Lee YC,Mukherjee AB

    更新日期：2006-06-01 00:00:00

  • An embryonic-like methylation pattern of classical satellite DNA is observed in ICF syndrome.

    abstract：:ICF syndrome has been described as the association of variable immunodeficiency, facial anomalies and centromeric heterochromatin instability. Since the chromosome rearrangements seen in cells of ICF patients are reminiscent of the chromosomal changes induced by the undermethylating agent 5-azacytidine in the late S-p...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/2.6.731

    authors： Jeanpierre M,Turleau C,Aurias A,Prieur M,Ledeist F,Fischer A,Viegas-Pequignot E

    更新日期：1993-06-01 00:00:00

  • Protecting genomic integrity during DNA replication: correlation between Werner's and Bloom's syndrome gene products and the MRE11 complex.

    abstract：:DNA replication is a critical step for cells because of the propensity of replication forks to stall, as a consequence either of endogenous DNA damage or of the propensity of repeated sequences to form tertiary structures, which can impede fork progression. Moreover, as a result of stalled replication fork processing,...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/11.20.2447

    authors： Franchitto A,Pichierri P

    更新日期：2002-10-01 00:00:00

  • The biological impact of blood pressure-associated genetic variants in the natriuretic peptide receptor C gene on human vascular smooth muscle.

    abstract：:Elevated blood pressure (BP) is a major global risk factor for cardiovascular disease. Genome-wide association studies have identified several genetic variants at the NPR3 locus associated with BP, but the functional impact of these variants remains to be determined. Here we confirmed, by a genome-wide association stu...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddx375

    authors： Ren M,Ng FL,Warren HR,Witkowska K,Baron M,Jia Z,Cabrera C,Zhang R,Mifsud B,Munroe PB,Xiao Q,Townsend-Nicholson A,Hobbs AJ,Ye S,Caulfield MJ

    更新日期：2018-01-01 00:00:00

  • Evaluating test statistics to select interesting genes in microarray experiments.

    abstract：:A randomization procedure to evaluate the significance level and the false-discovery rate in complex microarray experiments is proposed. A related graph can be used to compare different test statistics that can be used to analyze the same experiment. This graph is closely related to receiver operator characteristic (R...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/11.19.2223

    authors： Kooperberg C,Sipione S,LeBlanc M,Strand AD,Cattaneo E,Olson JM

    更新日期：2002-09-15 00:00:00

  • Improved imputation accuracy in Hispanic/Latino populations with larger and more diverse reference panels: applications in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

    abstract：:Imputation is commonly used in genome-wide association studies to expand the set of genetic variants available for analysis. Larger and more diverse reference panels, such as the final Phase 3 of the 1000 Genomes Project, hold promise for improving imputation accuracy in genetically diverse populations such as Hispani...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw174

    authors： Nelson SC,Stilp AM,Papanicolaou GJ,Taylor KD,Rotter JI,Thornton TA,Laurie CC

    更新日期：2016-08-01 00:00:00

  • Candidate DNA replication initiation regions at human trinucleotide repeat disease loci.

    abstract：:The positions of DNA replication initiation regions (IRs) at three human trinucleotide repeat (TNR) disease loci were examined in order to characterize the role played by IRs in explaining the known locus-specific variation in TNR instability levels. Using three different normal cell lines, candidate IRs were identifi...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg111

    authors： Nenguke T,Aladjem MI,Gusella JF,Wexler NS,Arnheim N,Venezuela HD Project.

    更新日期：2003-05-01 00:00:00

  • Rescue of cell death and inflammation of a mouse model of complex 1-mediated vision loss by repurposed drug molecules.

    abstract：:Inherited mitochondrial optic neuropathies, such as Leber's hereditary optic neuropathy (LHON) and Autosomal dominant optic atrophy (ADOA) are caused by mutant mitochondrial proteins that lead to defects in mitochondrial complex 1-driven ATP synthesis, and cause specific retinal ganglion cell (RGC) loss. Complex 1 def...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddx373

    authors： Yu AK,Datta S,McMackin MZ,Cortopassi GA

    更新日期：2017-12-15 00:00:00

  • Homozygous hereditary coproporphyria caused by an arginine to tryptophane substitution in coproporphyrinogen oxidase and common intragenic polymorphisms.

    abstract：:Coproporphyrinogen oxidase is a mitochondrial heme-biosynthetic enzyme that converts coproporphyrinogen to protoporphyrinogen. Inherited deficiency of this enzyme causes the human genetic disease hereditary coproporphyria. Recently, we isolated, sequenced and expressed the cDNA encoding human coproporphyrinogen oxidas...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/3.3.477

    authors： Martasek P,Nordmann Y,Grandchamp B

    更新日期：1994-03-01 00:00:00

  • Interaction between blood pressure quantitative trait loci in rats in which trait variation at chromosome 1 is conditional upon a specific allele at chromosome 10.

    abstract：:We have used inbred and congenic rat strains in F(2) segregation studies to discover epistasis in a polygenic model of hypertension. Previously, we have found evidence that the presence of a blood pressure quantitative trait locus (QTL) on chromosome 1 is conditional upon the allele status of chromosome 10. To prove t...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg041

    authors： Monti J,Plehm R,Schulz H,Ganten D,Kreutz R,Hübner N

    更新日期：2003-02-15 00:00:00

  • HACE1 is essential for astrocyte mitochondrial function and influences Huntington disease phenotypes in vivo.

    abstract：:Oxidative stress is a prominent feature of Huntington disease (HD), and we have shown previously that reduced levels of hace1 (HECT domain and Ankyrin repeat containing E3 ubiquitin protein ligase 1) in patient striatum may contribute to the pathogenesis of HD. Hace1 promotes the stability of Nrf2 and thus plays an im...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddx394

    authors： Ehrnhoefer DE,Southwell AL,Sivasubramanian M,Qiu X,Villanueva EB,Xie Y,Waltl S,Anderson L,Fazeli A,Casal L,Felczak B,Tsang M,Hayden MR

    更新日期：2018-01-15 00:00:00

  • FGFR2 regulates Mre11 expression and double-strand break repair via the MEK-ERK-POU1F1 pathway in breast tumorigenesis.

    abstract：:The association between breast cancer risk and genetic variants of fibroblast growth factor receptor 2 (FGFR2) has been identified and repeatedly confirmed; however, the mechanism underlying FGFR2 in breast tumorigenesis remains obscure. Given that breast tumorigenesis is particularly related to DNA double-strand-brea...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv102

    authors： Huang YL,Chou WC,Hsiung CN,Hu LY,Chu HW,Shen CY

    更新日期：2015-06-15 00:00:00

  • Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways.

    abstract：:Autism is a heterogeneous condition that is likely to result from the combined effects of multiple genetic factors interacting with environmental factors. Given its complexity, the study of autism associated with Mendelian single gene disorders or known chromosomal etiologies provides an important perspective. We used...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm116

    authors： Nishimura Y,Martin CL,Vazquez-Lopez A,Spence SJ,Alvarez-Retuerto AI,Sigman M,Steindler C,Pellegrini S,Schanen NC,Warren ST,Geschwind DH

    更新日期：2007-07-15 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

  • Allelic recombination and de novo deletions in sperm in the human beta-globin gene region.

    abstract：:Meiotic recombination is of fundamental importance in creating haplotype diversity in the human genome and has the potential to cause genomic rearrangements by ectopic recombination between repeat sequences and through other changes triggered by recombination-initiating events. However, the relationship between alleli...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddl025

    authors： Holloway K,Lawson VE,Jeffreys AJ

    更新日期：2006-04-01 00:00:00

  • Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease pathogenesis.

    abstract：:Huntington disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Although the mutant protein is widely expressed, the earliest and most striking neuropathological changes are observed in the striatum. Here we show dramatic mutation length increases (gai...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg352

    authors： Kennedy L,Evans E,Chen CM,Craven L,Detloff PJ,Ennis M,Shelbourne PF

    更新日期：2003-12-15 00:00:00

  • A small-molecule Nrf1 and Nrf2 activator mitigates polyglutamine toxicity in spinal and bulbar muscular atrophy.

    abstract：:Spinal and bulbar muscular atrophy (SBMA, also known as Kennedy's disease) is one of nine neurodegenerative disorders that are caused by expansion of polyglutamine-encoding CAG repeats. Intracellular accumulation of abnormal proteins in these diseases, a pathological hallmark, is associated with defects in protein hom...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw073

    authors： Bott LC,Badders NM,Chen KL,Harmison GG,Bautista E,Shih CC,Katsuno M,Sobue G,Taylor JP,Dantuma NP,Fischbeck KH,Rinaldi C

    更新日期：2016-05-15 00:00:00

  • Ca2+-permeable TRPV1 pain receptor knockout rescues memory deficits and reduces amyloid-β and tau in a mouse model of Alzheimer's disease.

    abstract：:The transient receptor potential vanilloid 1 (TRPV1) protein is a pain receptor that elicits a hot sensation when an organism eats the capsaicin of red chili peppers. This calcium (Ca2+)-permeable cation channel is mostly expressed in the peripheral nervous system sensory neurons but also in the central nervous system...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddz276

    authors： Kim J,Lee S,Kim J,Ham S,Park JHY,Han S,Jung YK,Shim I,Han JS,Lee KW,Kim J

    更新日期：2020-01-15 00:00:00

  • A feed-forward mechanism involving Drosophila fragile X mental retardation protein triggers a replication stress-induced DNA damage response.

    abstract：:Fragile X syndrome, a common form of inherited mental retardation, is caused by loss of the fragile X mental retardation protein (FMRP). As a selective RNA-binding protein, FMRP is localized predominately in cytoplasm, where it regulates translational control. However, there is a small portion of FMRP present in the n...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu241

    authors： Zhang W,Cheng Y,Li Y,Chen Z,Jin P,Chen D

    更新日期：2014-10-01 00:00:00