Viral delivery of glial cell line-derived neurotrophic factor improves behavior and protects striatal neurons in a mouse model of Huntington's disease.

Abstract:

:Huntington's disease (HD) is a fatal, genetic, neurological disorder resulting from a trinucleotide repeat expansion in the gene that encodes for the protein huntingtin. These excessive repeats confer a toxic gain of function on huntingtin, which leads to the degeneration of striatal and cortical neurons and a devastating motor, cognitive, and psychological disorder. Trophic factor administration has emerged as a compelling potential therapy for a variety of neurodegenerative disorders, including HD. We previously demonstrated that viral delivery of glial cell line-derived neurotrophic factor (GDNF) provides structural and functional neuroprotection in a rat neurotoxin model of HD. In this report we demonstrate that viral delivery of GDNF into the striatum of presymptomatic mice ameliorates behavioral deficits on the accelerating rotorod and hind limb clasping tests in transgenic HD mice. Behavioral neuroprotection was associated with anatomical preservation of the number and size of striatal neurons from cell death and cell atrophy. Additionally, GDNF-treated mice had a lower percentage of neurons containing mutant huntingtin-stained inclusion bodies, a hallmark of HD pathology. These data further support the concept that viral vector delivery of GDNF may be a viable treatment for patients suffering from HD.

authors

McBride JL,Ramaswamy S,Gasmi M,Bartus RT,Herzog CD,Brandon EP,Zhou L,Pitzer MR,Berry-Kravis EM,Kordower JH

doi

10.1073/pnas.0508875103

subject

Has Abstract

pub_date

2006-06-13 00:00:00

pages

9345-50

issue

24

eissn

0027-8424

issn

1091-6490

pii

0508875103

journal_volume

103

pub_type

杂志文章
  • Convergent and parallel activation of low-conductance potassium channels by calcium and cAMP-dependent protein kinase.

    abstract::K+ channels, which have been linked to regulation of electrogenic solute transport as well as Ca2+ influx, represent a locus in hepatocytes for the concerted actions of hormones that employ Ca2+ and cAMP as intracellular messengers. Despite considerable study, the single-channel basis for synergistic effects of Ca2+ a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.15.7115

    authors: Lidofsky SD

    更新日期:1995-07-18 00:00:00

  • RecA stimulates sister chromatid exchange and the fidelity of double-strand break repair, but not gene targeting, in plants transformed by Agrobacterium.

    abstract::Expression of the bacterial RecA protein in plants stimulates homologous recombination in tobacco. Here we show that RecA plays a direct role in DNA strand exchange in vivo. The number of sister chromatid exchanges (SCEs) was increased 2.4-fold over wild type in transgenic tobacco plants expressing a nuclear-targeted ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.050582797

    authors: Reiss B,Schubert I,Köpchen K,Wendeler E,Schell J,Puchta H

    更新日期:2000-03-28 00:00:00

  • A putative Ca2+-binding protein: structure of the light subunit of porcine calpain elucidated by molecular cloning and protein sequence analysis.

    abstract::cDNA clones specific for the light subunit of porcine calpain I have been isolated from a porcine kidney cDNA library. The complete primary structure of the light subunit has been revealed by nucleotide sequence analysis of the cDNA clones isolated and amino acid sequence analysis of peptides isolated from the purifie...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.18.6075

    authors: Sakihama T,Kakidani H,Zenita K,Yumoto N,Kikuchi T,Sasaki T,Kannagi R,Nakanishi S,Ohmori M,Takio K

    更新日期:1985-09-01 00:00:00

  • Dimerization of a viral SET protein endows its function.

    abstract::Histone modifications are regarded as the most indispensible phenomena in epigenetics. Of these modifications, lysine methylation is of the greatest complexity and importance as site- and state-specific lysine methylation exerts a plethora of effects on chromatin structure and gene transcription. Notably, paramecium b...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1009911107

    authors: Wei H,Zhou MM

    更新日期:2010-10-26 00:00:00

  • The C-terminal domain-phosphorylated IIO form of RNA polymerase II is associated with the transcription repressor NC2 (Dr1/DRAP1) and is required for transcription activation in human nuclear extracts.

    abstract::Activation of class II gene transcription may involve alleviation of transcription repression as well as stimulation of the assembly and function of the general RNA polymerase (RNAP) II transcription machinery. Here, we investigated whether activator-reversible transcription repression by NC2 (Dr1/DRAP1) contributes t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.140202297

    authors: Castaño E,Gross P,Wang Z,Roeder RG,Oelgeschläger T

    更新日期:2000-06-20 00:00:00

  • Maternal viral infection causes global alterations in porcine fetal microglia.

    abstract::Maternal infections during pregnancy are associated with increased risk of neurodevelopmental disorders, although the precise mechanisms remain to be elucidated. Previously, we established a maternal immune activation (MIA) model using swine, which results in altered social behaviors of piglet offspring. These behavio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1817014116

    authors: Antonson AM,Lawson MA,Caputo MP,Matt SM,Leyshon BJ,Johnson RW

    更新日期:2019-10-01 00:00:00

  • Cellular adaptation to opiates alters ion-channel mRNA levels.

    abstract::The chronic use of several drugs, including opiates, results in the stereotypical behaviors characteristic of addiction. Alterations in gene expression have been associated with the use of these addictive drugs. Previous studies, however, have been limited to describing changes in amounts of individual mRNAs from sing...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.1.385

    authors: Mackler SA,Eberwine JH

    更新日期:1994-01-04 00:00:00

  • Ubiquitous internal gene duplication and intron creation in eukaryotes.

    abstract::Duplication of genomic segments provides a primary resource for the origin of evolutionary novelties. However, most previous studies have focused on duplications of complete protein-coding genes, whereas little is known about the significance of duplication segments that are entirely internal to genes. Our examination...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0911093106

    authors: Gao X,Lynch M

    更新日期:2009-12-08 00:00:00

  • Reaction of glycolaldehyde with proteins: latent crosslinking potential of alpha-hydroxyaldehydes.

    abstract::The Schiff base adducts of glyceraldehyde with hemoglobin undergo Amadori rearrangement to form stable ketoamine structures; this reaction is similar to the nonenzymic glucosylation of proteins. In the present studies the analogous rearrangement of the Schiff base adducts of glycolaldehyde with proteins has been demon...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.12.3590

    authors: Acharya AS,Manning JM

    更新日期:1983-06-01 00:00:00

  • The genetic basis of a plant-insect coevolutionary key innovation.

    abstract::Ehrlich and Raven formally introduced the concept of stepwise coevolution using butterfly and angiosperm interactions in an attempt to account for the impressive biological diversity of these groups. However, many biologists currently envision butterflies evolving 50 to 30 million years (Myr) after the major angiosper...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0706229104

    authors: Wheat CW,Vogel H,Wittstock U,Braby MF,Underwood D,Mitchell-Olds T

    更新日期:2007-12-18 00:00:00

  • Proteomics approach to study the functions of Drosophila myosin VI through identification of multiple cargo-binding proteins.

    abstract::Myosin VI is a molecular motor implicated in many processes, and it likely associates with a variety of cargoes that specify its functions. Although it is critical to Drosophila development, little is known about its cellular roles. To reveal its involvement in specific pathways, we sought to identify the binding part...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1101415108

    authors: Finan D,Hartman MA,Spudich JA

    更新日期:2011-04-05 00:00:00

  • A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome.

    abstract::The T-box transcription factor TBX5 plays essential roles in cardiac and limb development. Various mutations in the TBX5 gene have been identified in patients with Holt-Oram syndrome, which is characterized by congenital defects in the heart and upper extremities. In this study, we identified a WW-domain-containing tr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0509109102

    authors: Murakami M,Nakagawa M,Olson EN,Nakagawa O

    更新日期:2005-12-13 00:00:00

  • The Opitz syndrome gene product, MID1, associates with microtubules.

    abstract::Opitz syndrome (OS) is a genetically heterogeneous disorder characterized by defects of the ventral midline, including hypertelorism, cleft lip and palate, heart defects, and mental retardation. We recently identified the gene responsible for X-linked OS. The ubiquitously expressed gene product, MID1, is a member of t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.6.2794

    authors: Schweiger S,Foerster J,Lehmann T,Suckow V,Muller YA,Walter G,Davies T,Porter H,van Bokhoven H,Lunt PW,Traub P,Ropers HH

    更新日期:1999-03-16 00:00:00

  • Cell-adhesion-disrupting action of interleukin 6 in human ductal breast carcinoma cells.

    abstract::Recombinant baculovirus-derived interleukin 6 (IL-6) disrupts the attachment of human ductal breast carcinoma subline ZR-75-1-Tx cells to neighbors and the substratum in culture without inhibiting the proliferation of the cells. The nonadherent cells lack pseudopodia and do not translocate directionally. These finding...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.8.3329

    authors: Tamm I,Kikuchi T,Cardinale I,Krueger JG

    更新日期:1994-04-12 00:00:00

  • Transdominant genetic analysis of a growth control pathway.

    abstract::Genetic selections that use proteinaceous transdominant inhibitors encoded by DNA libraries to cause mutant phenocopies may facilitate genetic analysis in traditionally nongenetic organisms. We performed a selection for random short peptides and larger protein fragments (collectively termed "perturbagens") that inhibi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.13.7508

    authors: Caponigro G,Abedi MR,Hurlburt AP,Maxfield A,Judd W,Kamb A

    更新日期:1998-06-23 00:00:00

  • Brief visual experience induces immediate early gene expression in the cat visual cortex.

    abstract::Brief visual experience causes rapid physiological changes in the visual cortex during early postnatal development. A possible mediator of these effects is the immediate early genes whose protein products are involved in the rapid response of neurons to transsynaptic stimulation. Here we report evidence that the level...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.12.5437

    authors: Rosen KM,McCormack MA,Villa-Komaroff L,Mower GD

    更新日期:1992-06-15 00:00:00

  • Influenza hemagglutinin drives viral entry via two sequential intramembrane mechanisms.

    abstract::Enveloped viruses enter cells via a process of membrane fusion between the viral envelope and a cellular membrane. For influenza virus, mutational data have shown that the membrane-inserted portions of the hemagglutinin protein play a critical role in achieving fusion. In contrast to the relatively well-understood ect...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1914188117

    authors: Pabis A,Rawle RJ,Kasson PM

    更新日期:2020-03-31 00:00:00

  • The oldest modern therian mammal from Europe and its bearing on stem marsupial paleobiogeography.

    abstract::We report the discovery of mammalian tribosphenic teeth from the basal Cenomanian of southwestern France that we refer to a new primitive marsupial-like form identified as a basal taxon of Marsupialiformes, a new clade recognized here to include the crown group Marsupialia and primitive stem lineages more closely rela...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0902940106

    authors: Vullo R,Gheerbrant E,de Muizon C,Néraudeau D

    更新日期:2009-11-24 00:00:00

  • Erythropoietin induces tumor regression and antitumor immune responses in murine myeloma models.

    abstract::Recombinant human erythropoietin (rHuEpo) has been used successfully in the treatment of cancer-related anemia. Clinical observations with several patients with multiple-myeloma treated with rHuEpo has shown, in addition to the improved quality of life, a longer survival than expected, considering the poor prognostic ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.081275298

    authors: Mittelman M,Neumann D,Peled A,Kanter P,Haran-Ghera N

    更新日期:2001-04-24 00:00:00

  • Dysregulation of signaling pathways in CD45-deficient NK cells leads to differentially regulated cytotoxicity and cytokine production.

    abstract::CD45, a protein tyrosine phosphatase that regulates Src family kinases, is important for regulating T cell and B cell receptor signaling; however, little is known about how CD45 regulates immunoreceptor tyrosine-based activation motif (ITAM)-dependent natural killer (NK) cell receptor signaling and the resulting effec...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0601851103

    authors: Hesslein DG,Takaki R,Hermiston ML,Weiss A,Lanier LL

    更新日期:2006-05-02 00:00:00

  • CD83-stimulated monocytes suppress T-cell immune responses through production of prostaglandin E2.

    abstract::CD83 is commonly known as a specific marker for mature dendritic cells. It has been shown to be important for CD4(+) T-cell development in the thymus. However, its function in the peripheral immune system remains enigmatic. Here, we show that CD83 inhibits proliferation and production of IL-2 and IFN-γ by T cells, and...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1018994108

    authors: Chen L,Zhu Y,Zhang G,Gao C,Zhong W,Zhang X

    更新日期:2011-11-15 00:00:00

  • Refinement of the X-ray Structure of Rubredoxin by Conformational Energy Calculations.

    abstract::The x-ray structure of rubredoxin has been refined by energy minimization. The computed structure is constrained to have standard bond lengths, bond angles, and planar trans peptide groups. Also, since most of the steric overlaps have been relieved, it has a very low energy. As judged by the root mean square (RMS) dev...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.9.3736

    authors: Rasse D,Warme PK,Scheraga HA

    更新日期:1974-09-01 00:00:00

  • Resistance to juvenile hormone and an insect growth regulator in Drosophila is associated with an altered cytosolic juvenile hormone-binding protein.

    abstract::The Met mutant of Drosophila melanogaster is highly resistant to juvenile hormone III (JH III) or its chemical analog, methoprene, an insect growth regulator. Five major mechanisms of insecticide resistance were examined in Met and susceptible Met+ flies. These two strains showed only minor differences when penetratio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.6.2072

    authors: Shemshedini L,Wilson TG

    更新日期:1990-03-01 00:00:00

  • Microparadigms: chains of collective reasoning in publications about molecular interactions.

    abstract::We analyzed a very large set of molecular interactions that had been derived automatically from biological texts. We found that published statements, regardless of their verity, tend to interfere with interpretation of the subsequent experiments and, therefore, can act as scientific "microparadigms," similar to domina...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0600591103

    authors: Rzhetsky A,Iossifov I,Loh JM,White KP

    更新日期:2006-03-28 00:00:00

  • Lon-dependent regulation of the DNA binding protein HU in Escherichia coli.

    abstract::HU, the major DNA binding protein of Escherichia coli, exists in solution as a heterodimer composed of two highly homologous subunits: HU1, encoded by hupB; HU2, encoded by hupA. The purification of the HU protein from hupA- or hupB- bacteria showed that the hupB mutant strains synthesize normal amounts of the HU2 sub...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.20.7691

    authors: Bonnefoy E,Almeida A,Rouviere-Yaniv J

    更新日期:1989-10-01 00:00:00

  • Sterigmatocystin-DNA interactions: identification of a major adduct formed after metabolic activation in vitro.

    abstract::Sterigmatocystin (ST), a potent hepatocarcinogen, was covalently bound to calf thymus DNA by incubation in the presence of phenobarbital-induced rat liver microsomes. Acid hydrolysis of ST-modified DNA liberated a major guanine-containing adduct, present in DNA at an estimated level of 1 ST residue per 100-150 nucleot...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.1.179

    authors: Essigmann JM,Barker LJ,Fowler KW,Francisco MA,Reinhold VN,Wogan GN

    更新日期:1979-01-01 00:00:00

  • Selectivity at the cleavage/attachment site of phosphatidylinositol-glycan anchored membrane proteins is enzymatically determined.

    abstract::Nascent precursors of phosphatidylinositol-glycan (PI-G)-linked membrane proteins contain a hydrophobic COOH-terminal sequence of 15-30 residues that is eliminated during processing to yield a newly exposed COOH terminus to which the PI-G moiety is added. There is no consensus as to the primary structure of the termin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.20.7939

    authors: Micanovic R,Kodukula K,Gerber LD,Udenfriend S

    更新日期:1990-10-01 00:00:00

  • Specificity in the activation and control of transcription factor E2F-dependent apoptosis.

    abstract::Previous work has demonstrated a role for the E2F1 gene product in signaling apoptosis, both as a result of the deregulation of the Rb/E2F pathway as well as in response to DNA damage. We now show that the ability of cells to suppress the apoptotic potential of E2F1, as might occur during the course of normal cellular...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1831408100

    authors: Hallstrom TC,Nevins JR

    更新日期:2003-09-16 00:00:00

  • Sorting-out of acceptor-donor relationships in the transglutaminase-catalyzed cross-linking of crystallins by the enzyme-directed labeling of potential sites.

    abstract::The dansyl-conjugated (Dns) peptides Dns-Pro-Gly-Gly-Gln-Gln-Ile-Val and Dns-Ala-Gln-Gln-Ile-Val, patterned on the N-terminal sequence of fibronectin, were synthesized and used for the transglutaminase (protein-glutamine:amine gamma-glutamyltransferase, EC 2.3.2.13)-directed selective blocking of lens proteins that ot...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.1.82

    authors: Lorand L,Parameswaran KN,Velasco PT

    更新日期:1991-01-01 00:00:00

  • Interaction of an NF-kappa B-like factor with a site upstream of the c-myc promoter.

    abstract::The c-myc protooncogene has been implicated in control of growth and differentiation of mammalian cells. For instance, growth arrest is often preceded by reduction in c-myc mRNA and gene transcription. To elucidate the mechanisms of control of c-myc gene transcription, we have begun to characterize the interaction of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.12.4727

    authors: Duyao MP,Buckler AJ,Sonenshein GE

    更新日期:1990-06-01 00:00:00