Literature DB >> 25062765

Rhes suppression enhances disease phenotypes in Huntington's disease mice.

John H Lee1, Matthew J Sowada2, Ryan L Boudreau2, Andrea M Aerts3, Daniel R Thedens4, Peg Nopoulos3, Beverly L Davidson5.   

Abstract

In Huntington's disease (HD) mutant HTT is ubiquitously expressed yet the striatum undergoes profound early degeneration. Cell culture studies suggest that a striatal-enriched protein, Rhes, may account for this vulnerability. We investigated the therapeutic potential of silencing Rhes in vivo using inhibitory RNAs (miRhes). While Rhes suppression was tolerated in wildtype mice, it failed to improve rotarod function in two distinct HD mouse models. Additionally, miRhes treated HD mice had increased anxiety-like behaviors and enhanced striatal atrophy as measured by longitudinal MRI when compared to control treated mice. These findings raise caution regarding the long-term implementation of inhibiting Rhes as a therapy for HD.

Entities:  

Keywords:  Huntington disease; RNA interference; Rhes; genetic therapies; neurodegenerative disease; rasd2

Mesh：

Substances：

Year:  2014        PMID： 25062765      PMCID： PMC4139702          DOI： 10.3233/JHD-140094

Source DB:  PubMed          Journal:  J Huntingtons Dis        ISSN： 1879-6397


  28 in total

1.  RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model.

Authors:  Scott Q Harper; Patrick D Staber; Xiaohua He; Steven L Eliason; Inês H Martins; Qinwen Mao; Linda Yang; Robert M Kotin; Henry L Paulson; Beverly L Davidson
Journal:  Proc Natl Acad Sci U S A       Date:  2005-04-05       Impact factor: 11.205

2.  Thyroid hormone regulation of rhes, a novel Ras homolog gene expressed in the striatum.

Authors:  P Vargiu; B Morte; J Manzano; J Perez; R de Abajo; J Gregor Sutcliffe; J Bernal
Journal:  Brain Res Mol Brain Res       Date:  2001-10-19

3.  Rhes is involved in striatal function.

Authors:  Daniela Spano; Igor Branchi; Annamaria Rosica; Maria Teresa Pirro; Antonio Riccio; Pratibha Mithbaokar; Andrea Affuso; Claudio Arra; Patrizia Campolongo; Daniela Terracciano; Vincenzo Macchia; Juan Bernal; Enrico Alleva; Roberto Di Lauro
Journal:  Mol Cell Biol       Date:  2004-07       Impact factor: 4.272

4.  Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease.

Authors:  Brinda Ravikumar; Coralie Vacher; Zdenek Berger; Janet E Davies; Shouqing Luo; Lourdes G Oroz; Francesco Scaravilli; Douglas F Easton; Rainer Duden; Cahir J O'Kane; David C Rubinsztein
Journal:  Nat Genet       Date:  2004-05-16       Impact factor: 38.330

Review 5.  Mutant huntingtin can paradoxically protect neurons from death.

Authors:  T Zuchner; P Brundin
Journal:  Cell Death Differ       Date:  2007-11-02       Impact factor: 15.828

6.  Regional and cellular gene expression changes in human Huntington's disease brain.

Authors:  Angela Hodges; Andrew D Strand; Aaron K Aragaki; Alexandre Kuhn; Thierry Sengstag; Gareth Hughes; Lyn A Elliston; Cathy Hartog; Darlene R Goldstein; Doris Thu; Zane R Hollingsworth; Francois Collin; Beth Synek; Peter A Holmans; Anne B Young; Nancy S Wexler; Mauro Delorenzi; Charles Kooperberg; Sarah J Augood; Richard L M Faull; James M Olson; Lesley Jones; Ruth Luthi-Carter
Journal:  Hum Mol Genet       Date:  2006-02-08       Impact factor: 6.150

7.  Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi.

Authors:  Jodi L McBride; Ryan L Boudreau; Scott Q Harper; Patrick D Staber; Alex Mas Monteys; Inâs Martins; Brian L Gilmore; Haim Burstein; Richard W Peluso; Barry Polisky; Barrie J Carter; Beverly L Davidson
Journal:  Proc Natl Acad Sci U S A       Date:  2008-04-08       Impact factor: 11.205

8.  Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin.

Authors:  G Schilling; M W Becher; A H Sharp; H A Jinnah; K Duan; J A Kotzuk; H H Slunt; T Ratovitski; J K Cooper; N A Jenkins; N G Copeland; D L Price; C A Ross; D R Borchelt
Journal:  Hum Mol Genet       Date:  1999-03       Impact factor: 6.150

9.  Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice.

Authors:  Michelle Gray; Dyna I Shirasaki; Carlos Cepeda; Véronique M André; Brian Wilburn; Xiao-Hong Lu; Jifang Tao; Irene Yamazaki; Shi-Hua Li; Yi E Sun; Xiao-Jiang Li; Michael S Levine; X William Yang
Journal:  J Neurosci       Date:  2008-06-11       Impact factor: 6.167

10.  Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway.

Authors:  Ai Yamamoto; M Laura Cremona; James E Rothman
Journal:  J Cell Biol       Date:  2006-02-27       Impact factor: 10.539
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  8 in total

1.  Reinstating aberrant mTORC1 activity in Huntington's disease mice improves disease phenotypes.

Authors:  John H Lee; Luis Tecedor; Yong Hong Chen; Alex Mas Monteys; Matthew J Sowada; Leslie M Thompson; Beverly L Davidson
Journal:  Neuron       Date:  2014-12-31       Impact factor: 17.173

2.  Self-Complementary AAV9 Gene Delivery Partially Corrects Pathology Associated with Juvenile Neuronal Ceroid Lipofuscinosis (CLN3).

Authors:  Megan E Bosch; Amy Aldrich; Rachel Fallet; Jessica Odvody; Maria Burkovetskaya; Kaitlyn Schuberth; Julie A Fitzgerald; Kevin D Foust; Tammy Kielian
Journal:  J Neurosci       Date:  2016-09-14       Impact factor: 6.167

3.  Loss of Hap1 selectively promotes striatal degeneration in Huntington disease mice.

Authors:  Qiong Liu; Siying Cheng; Huiming Yang; Louyin Zhu; Yongcheng Pan; Liang Jing; Beisha Tang; Shihua Li; Xiao-Jiang Li
Journal:  Proc Natl Acad Sci U S A       Date:  2020-08-03       Impact factor: 11.205

Review 4.  Cell-Autonomous and Non-cell-Autonomous Pathogenic Mechanisms in Huntington's Disease: Insights from In Vitro and In Vivo Models.

Authors:  Jordi Creus-Muncunill; Michelle E Ehrlich
Journal:  Neurotherapeutics       Date:  2019-10       Impact factor: 7.620

Review 5.  Striatal Vulnerability in Huntington's Disease: Neuroprotection Versus Neurotoxicity.

Authors:  Ryoma Morigaki; Satoshi Goto
Journal:  Brain Sci       Date:  2017-06-07

6.  Bioinformatics analysis of Ras homologue enriched in the striatum, a potential target for Huntington's disease therapy.

Authors:  Miriam Carbo; Valentina Brandi; Gianmarco Pascarella; David Sasah Staid; Gianni Colotti; Fabio Polticelli; Andrea Ilari; Veronica Morea
Journal:  Int J Mol Med       Date:  2019-10-15       Impact factor: 4.101

Review 7.  D1R- and D2R-Medium-Sized Spiny Neurons Diversity: Insights Into Striatal Vulnerability to Huntington's Disease Mutation.

Authors:  Guendalina Bergonzoni; Jessica Döring; Marta Biagioli
Journal:  Front Cell Neurosci       Date:  2021-02-10       Impact factor: 5.505

8.  Huntington's disease phenotypes are improved via mTORC1 modulation by small molecule therapy.

Authors:  Sophie St-Cyr; Daniel D Child; Emilie Giaime; Alicia R Smith; Christine J Pascua; Seung Hahm; Eddine Saiah; Beverly L Davidson
Journal:  PLoS One       Date:  2022-08-29       Impact factor: 3.752
  8 in total

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