HDAC4 Reduction: A Novel Therapeutic Strategy to Target Cytoplasmic Huntingtin and Ameliorate Neurodegeneration
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{"title"=>"HDAC4 Reduction: A Novel Therapeutic Strategy to Target Cytoplasmic Huntingtin and Ameliorate Neurodegeneration", "type"=>"journal", "authors"=>[{"first_name"=>"Michal", "last_name"=>"Mielcarek", "scopus_author_id"=>"7003373406"}, {"first_name"=>"Christian", "last_name"=>"Landles", "scopus_author_id"=>"8940145800"}, {"first_name"=>"Andreas", "last_name"=>"Weiss", "scopus_author_id"=>"15021604600"}, {"first_name"=>"Amyaouch", "last_name"=>"Bradaia", "scopus_author_id"=>"6603188948"}, {"first_name"=>"Tamara", "last_name"=>"Seredenina", "scopus_author_id"=>"10541035600"}, {"first_name"=>"Linda", "last_name"=>"Inuabasi", "scopus_author_id"=>"55948518000"}, {"first_name"=>"Georgina F.", "last_name"=>"Osborne", "scopus_author_id"=>"55948839800"}, {"first_name"=>"Kristian", "last_name"=>"Wadel", "scopus_author_id"=>"15840914400"}, {"first_name"=>"Chrystelle", "last_name"=>"Touller", "scopus_author_id"=>"55535053200"}, {"first_name"=>"Rachel", "last_name"=>"Butler", "scopus_author_id"=>"57196325914"}, {"first_name"=>"Janette", "last_name"=>"Robertson", "scopus_author_id"=>"57197258244"}, {"first_name"=>"Sophie A.", "last_name"=>"Franklin", "scopus_author_id"=>"54781238700"}, {"first_name"=>"Donna L.", "last_name"=>"Smith", "scopus_author_id"=>"7410356859"}, {"first_name"=>"Larry", "last_name"=>"Park", "scopus_author_id"=>"37002099300"}, {"first_name"=>"Paul A.", "last_name"=>"Marks", "scopus_author_id"=>"7101844468"}, {"first_name"=>"Erich E.", "last_name"=>"Wanker", "scopus_author_id"=>"7004017730"}, {"first_name"=>"Eric N.", "last_name"=>"Olson", "scopus_author_id"=>"35393950100"}, {"first_name"=>"Ruth", "last_name"=>"Luthi-Carter", "scopus_author_id"=>"6602843291"}, {"first_name"=>"Herman", "last_name"=>"van der Putten", "scopus_author_id"=>"7004535182"}, {"first_name"=>"Vahri", "last_name"=>"Beaumont", "scopus_author_id"=>"7006007144"}, {"first_name"=>"Gillian P.", "last_name"=>"Bates", "scopus_author_id"=>"35380748900"}], "year"=>2013, "source"=>"PLoS Biology", "identifiers"=>{"pui"=>"370401991", "sgr"=>"84889031644", "issn"=>"15449173", "pmid"=>"24302884", "scopus"=>"2-s2.0-84889031644", "doi"=>"10.1371/journal.pbio.1001717", "isbn"=>"1545-7885"}, "id"=>"4a800a61-2179-338b-8de8-9982e6d0071b", "abstract"=>"Histone deacetylase (HDAC) 4 is a transcriptional repressor that contains a glutamine-rich domain. We hypothesised that it may be involved in the molecular pathogenesis of Huntington's disease (HD), a protein-folding neurodegenerative disorder caused by an aggregation-prone polyglutamine expansion in the huntingtin protein. We found that HDAC4 associates with huntingtin in a polyglutamine-length-dependent manner and co-localises with cytoplasmic inclusions. We show that HDAC4 reduction delayed cytoplasmic aggregate formation, restored Bdnf transcript levels, and rescued neuronal and cortico-striatal synaptic function in HD mouse models. This was accompanied by an improvement in motor coordination, neurological phenotypes, and increased lifespan. Surprisingly, HDAC4 reduction had no effect on global transcriptional dysfunction and did not modulate nuclear huntingtin aggregation. Our results define a crucial role for the cytoplasmic aggregation process in the molecular pathology of HD. HDAC4 reduction presents a novel strategy for targeting huntingtin aggregation, which may be amenable to small-molecule therapeutics.", "link"=>"http://www.mendeley.com/research/hdac4-reduction-novel-therapeutic-strategy-target-cytoplasmic-huntingtin-ameliorate-neurodegeneratio", "reader_count"=>94, "reader_count_by_academic_status"=>{"Unspecified"=>7, "Professor > Associate Professor"=>5, "Researcher"=>25, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>22, "Student > Postgraduate"=>3, "Student > Master"=>11, "Other"=>6, "Student > Bachelor"=>12, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>7, "Professor > Associate Professor"=>5, "Researcher"=>25, "Student > Doctoral Student"=>2, "Student > Ph. D. 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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1296007", "https://ndownloader.figshare.com/files/1296008", "https://ndownloader.figshare.com/files/1296009", "https://ndownloader.figshare.com/files/1296010", "https://ndownloader.figshare.com/files/1296011", "https://ndownloader.figshare.com/files/1296012", "https://ndownloader.figshare.com/files/1296013", "https://ndownloader.figshare.com/files/1296014", "https://ndownloader.figshare.com/files/1296015", "https://ndownloader.figshare.com/files/1296016"], "description"=>"<div><p>Histone deacetylase (HDAC) 4 is a transcriptional repressor that contains a glutamine-rich domain. We hypothesised that it may be involved in the molecular pathogenesis of Huntington's disease (HD), a protein-folding neurodegenerative disorder caused by an aggregation-prone polyglutamine expansion in the huntingtin protein. We found that HDAC4 associates with huntingtin in a polyglutamine-length-dependent manner and co-localises with cytoplasmic inclusions. We show that HDAC4 reduction delayed cytoplasmic aggregate formation, restored <i>Bdnf</i> transcript levels, and rescued neuronal and cortico-striatal synaptic function in HD mouse models. This was accompanied by an improvement in motor coordination, neurological phenotypes, and increased lifespan. Surprisingly, HDAC4 reduction had no effect on global transcriptional dysfunction and did not modulate nuclear huntingtin aggregation. Our results define a crucial role for the cytoplasmic aggregation process in the molecular pathology of HD. HDAC4 reduction presents a novel strategy for targeting huntingtin aggregation, which may be amenable to small-molecule therapeutics.</p></div>", "links"=>[], "tags"=>["therapeutic", "cytoplasmic", "huntingtin", "ameliorate"], "article_id"=>862746, "categories"=>["Uncategorised"], "users"=>["Michal Mielcarek", "Christian Landles", "Andreas Weiss", "Amyaouch Bradaia", "Tamara Seredenina", "Linda Inuabasi", "Georgina F. Osborne", "Kristian Wadel", "Chrystelle Touller", "Rachel Butler", "Janette Robertson", "Sophie A. Franklin", "Donna L. Smith", "Larry Park", "Paul A. Marks", "Erich E. Wanker", "Eric N. Olson", "Ruth Luthi-Carter", "Herman van der Putten", "Vahri Beaumont", "Gillian P. Bates"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001717.s001", "https://dx.doi.org/10.1371/journal.pbio.1001717.s002", "https://dx.doi.org/10.1371/journal.pbio.1001717.s003", "https://dx.doi.org/10.1371/journal.pbio.1001717.s004", "https://dx.doi.org/10.1371/journal.pbio.1001717.s005", "https://dx.doi.org/10.1371/journal.pbio.1001717.s006", "https://dx.doi.org/10.1371/journal.pbio.1001717.s007", "https://dx.doi.org/10.1371/journal.pbio.1001717.s008", "https://dx.doi.org/10.1371/journal.pbio.1001717.s009", "https://dx.doi.org/10.1371/journal.pbio.1001717.s010"], "stats"=>{"downloads"=>24, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HDAC4_Reduction_A_Novel_Therapeutic_Strategy_to_Target_Cytoplasmic_Huntingtin_and_Ameliorate_Neurodegeneration_/862746", "title"=>"HDAC4 Reduction: A Novel Therapeutic Strategy to Target Cytoplasmic Huntingtin and Ameliorate Neurodegeneration", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-11-26 03:44:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1296002"], "description"=>"<p>(A) Seprion ligand ELISA was used to quantify aggregate load in the cortex of R6/2 and Dble::R6/2 mice at 4, 9, and 15 wk of age. Values for the Dble::R6/2 mice were plotted as a percentage of R6/2 aggregate load (<i>n</i> = 6). (B) TR-FRET was used to determine the levels of soluble exon 1 HTT in the cortex of R6/2 and Dble::R6/2 mice at 4, 9, and 15 wk of age (<i>n</i> = 6). (C) Seprion ligand ELISA was used to quantify aggregate load in the striatum, cortex, and cerebellum of <i>Hdh</i>Q150 and Dble::<i>Hdh</i>Q150 mice at 6 and 10 mo of age. Values for the Dble::<i>Hdh</i>Q150 mice were plotted as a percentage of aggregate load of <i>Hdh</i>Q150 mice (<i>n</i>≥7). (D) Representative S830 immunoblot of cortical lysates showing the difference in soluble and aggregated exon 1 HTT between R6/2 and Dble::R6/2 (Dble) mice and how this change occurs with age. (E) Comparison of HDAC4 levels in the nuclear and cytoplasmic fractions of R6/2 and Dble::R6/2 (Dble) brains by western blot. The purity of the fractions is shown in <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001717#pbio.1001717.s002\" target=\"_blank\">Figure S2D</a>. (F) Western blot of detergent-insoluble high molecular weight (HMW) aggregates isolated from the nuclear and cytoplasmic fractions of R6/2 and Dble::R6/2 (Dble) brains, resolved by agarose gel electrophoresis (AGERA), and immunodetected with the S830 antibody (representative of three experiments) (<i>n</i> = 8). The purity of the fractions is shown by western blotting with α-tubulin and histone H3. (G) Western blot of HDAC4 in the cytoplasmic fraction of R6/2 and Dble::R6/2 (Dble) brains at 9 wk of age. HDAC4 levels were measured by densitometry and calculated relative to α-tubulin. Error bars are SEM. <i>p</i> values were calculated using Student's <i>t</i> test.</p>", "links"=>[], "tags"=>["knock-down", "delays", "aggregate"], "article_id"=>862741, "categories"=>["Uncategorised"], "users"=>["Michal Mielcarek", "Christian Landles", "Andreas Weiss", "Amyaouch Bradaia", "Tamara Seredenina", "Linda Inuabasi", "Georgina F. Osborne", "Kristian Wadel", "Chrystelle Touller", "Rachel Butler", "Janette Robertson", "Sophie A. Franklin", "Donna L. Smith", "Larry Park", "Paul A. Marks", "Erich E. Wanker", "Eric N. Olson", "Ruth Luthi-Carter", "Herman van der Putten", "Vahri Beaumont", "Gillian P. Bates"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001717.g002", "stats"=>{"downloads"=>0, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HDAC4_knock_down_delays_aggregate_formation_in_R6_2_and_Hdh_Q150_mouse_models_of_HD_/862741", "title"=>"HDAC4 knock-down delays aggregate formation in R6/2 and <i>Hdh</i>Q150 mouse models of HD.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-26 03:44:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1296001"], "description"=>"<p>(A) Breeding scheme used to reduce <i>Hdac4</i> levels in both R6/2 and heterozygous <i>Hdh</i>Q150 mice. WT, wild type; <i>Hdac4</i>HET, <i>Hdac4</i>KO heterozygotes; Dble::R6/2, R6/2 mice heterozygous for <i>Hdac4</i>KO; Dble::<i>Hdh</i>Q150, <i>Hdh</i>Q150 mice heterozygous for <i>Hdac4</i>KO. (B) <i>Hdac</i>4 transcript levels were decreased in <i>Hdac</i>4HET, Dble::R6/2, and Dble::<i>Hdh</i>Q150 mice as measured by Taqman qPCR. (C) Taqman qPCR showed that <i>HTT</i> exon 1 transgene levels did not differ between R6/2 and Dble::R6/2 mice. (D) Taqman qPCR showed that the expression of endogenous <i>Htt</i> was equivalent between WT and <i>Hdac4</i>HETs and did not change when <i>Hdac4</i> was knocked down in R6/2 or <i>Hdh</i>Q150 mice. (E) The transcript levels of other <i>Hdacs</i> were equivalent to WT levels in <i>Hdac</i>4HET, R6/2, and Dble::R6/2 mice as determined by Taqman qPCR. All Taqman qPCR values were normalized to the geometric mean of three housekeeping genes: <i>Atp5b</i>, <i>Canx</i>, and <i>Rpl13a</i>. Error bars are SEM using Student's <i>t</i> test (<i>n</i> = 8). **<i>p</i><0.01; ***<i>p</i><0.001.</p>", "links"=>[], "tags"=>["exon", "endogenous"], "article_id"=>862740, "categories"=>["Uncategorised"], "users"=>["Michal Mielcarek", "Christian Landles", "Andreas Weiss", "Amyaouch Bradaia", "Tamara Seredenina", "Linda Inuabasi", "Georgina F. Osborne", "Kristian Wadel", "Chrystelle Touller", "Rachel Butler", "Janette Robertson", "Sophie A. Franklin", "Donna L. Smith", "Larry Park", "Paul A. Marks", "Erich E. Wanker", "Eric N. Olson", "Ruth Luthi-Carter", "Herman van der Putten", "Vahri Beaumont", "Gillian P. Bates"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001717.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hdac4_reduction_does_not_alter_the_expression_levels_of_HTT_exon_1_endogenous_Htt_or_other_Hdacs_/862740", "title"=>"<i>Hdac4</i> reduction does not alter the expression levels of <i>HTT</i> exon 1, endogenous <i>Htt</i>, or other <i>Hdacs</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-26 03:44:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1296006"], "description"=>"<p>(A) Reduction in HDAC4 results in a pronounced delay in impaired motor coordination as determined by rotarod performance (<i>n</i>≥13/genotype). (B) Assessment of neurological phenotypes via a modified SHIRPA protocol (see <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001717#pbio.1001717.s005\" target=\"_blank\">Table S2</a> for details). Of the nine parameters that distinguished R6/2 and WT mice, all were improved in the Dble::R6/2 mice. See also <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001717#pbio.1001717.s009\" target=\"_blank\">Video S1</a> and <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001717#pbio.1001717.s010\" target=\"_blank\">Video S2</a>. (C) Kaplan–Meier analysis showed that knock-down of HDAC4 significantly increased R6/2 survival (<i>n</i>≥13/genotype). (D) Reduction of HDAC4 did not result in an overall improvement in the failure of R6/2 mice to gain weight, although Dble::R6/2 mice were significantly heavier than R6/2 mice at 15 wk of age (<i>n</i>≥13/genotype). (E) There was a slight but statistically significant increase in the brain weight of Dble::R6/2 as compared to R6/2 mice at 4 and 9 wk of age (<i>n</i>≥10/genotype). Statistical analysis was performed by GLM-ANOVA with Greenhouse Geisser <i>post hoc</i> analysis (B and D), by multiple comparisons using Bonferroni post hoc test (B and D), and by log-rank test (C).</p>", "links"=>[], "tags"=>["knock-down", "improves", "neurological", "phenotypes", "extends"], "article_id"=>862745, "categories"=>["Uncategorised"], "users"=>["Michal Mielcarek", "Christian Landles", "Andreas Weiss", "Amyaouch Bradaia", "Tamara Seredenina", "Linda Inuabasi", "Georgina F. Osborne", "Kristian Wadel", "Chrystelle Touller", "Rachel Butler", "Janette Robertson", "Sophie A. Franklin", "Donna L. Smith", "Larry Park", "Paul A. Marks", "Erich E. Wanker", "Eric N. Olson", "Ruth Luthi-Carter", "Herman van der Putten", "Vahri Beaumont", "Gillian P. Bates"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001717.g006", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HDAC4_knock_down_improves_neurological_phenotypes_and_extends_survival_/862745", "title"=>"HDAC4 knock-down improves neurological phenotypes and extends survival.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-26 03:44:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1296004"], "description"=>"<p>(A) Affymetrix arrays were used to determine the effect of <i>Hdac4</i> knock-down on the cortical transcription profile of WT and R6/2 mice at 9 and 15 wk of age (<i>n</i>≥8 per genotype per time point). The number of genes that were significantly altered between genotypes with a fold-change of >30% for each pairwise comparison is noted. Statistical significance was determined after FDR-correction at a stringency of <i>p</i>≤0.05. (B) Taqman qPCR validation of the genes that were predicted to be differentially expressed between R6/2 and Dble::R6/2 cortex at 9 wk of age. See <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001717#pbio.1001717.s006\" target=\"_blank\">Table S3</a> for gene abbreviation definitions. (C) Cortical <i>Bdnf</i> mRNA levels for promoter transcripts 1, 2a, 4, and 5 as well as the coding exon (B) were assessed by Taqman qPCR at 15 wk of age. All Taqman qPCR values were normalized to the geometric mean of three housekeeping genes: <i>Atp5b</i>, <i>Canx</i>, and <i>Rpl13a</i>. Error bars are S.E.M (<i>n</i> = 8). *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001; NS, not significant.</p>", "links"=>[], "tags"=>["knock-down", "transcriptional"], "article_id"=>862743, "categories"=>["Uncategorised"], "users"=>["Michal Mielcarek", "Christian Landles", "Andreas Weiss", "Amyaouch Bradaia", "Tamara Seredenina", "Linda Inuabasi", "Georgina F. Osborne", "Kristian Wadel", "Chrystelle Touller", "Rachel Butler", "Janette Robertson", "Sophie A. Franklin", "Donna L. Smith", "Larry Park", "Paul A. Marks", "Erich E. Wanker", "Eric N. Olson", "Ruth Luthi-Carter", "Herman van der Putten", "Vahri Beaumont", "Gillian P. Bates"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001717.g004", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HDAC4_knock_down_does_not_rescue_global_transcriptional_dysregulation_/862743", "title"=>"HDAC4 knock-down does not rescue global transcriptional dysregulation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-26 03:44:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1296005"], "description"=>"<p>(A–H) Box and whisker plots of (A, E) input resistance (R<sub>m</sub>), (B, F) RMP, (C, G) rheobase current, and (D, H) spike amplitude from corticostriatal slices at (A–D) 7–8 and (E–H) 12 wk of age. Box and whisker plots: +, mean; box, interquartile range; whisker, 10–90 percentile; outliers, closed circles. (I) Measurement of evoked EPSCs following cortical stimulation showed that the R6/2 mice show lower basal transmission compared to WT or <i>Hdac4</i>HET and that this is restored in the Dble::R6/2 mice at 7–12 wk of age. (J) R6/2 MSNs have a higher paired-pulse ratio than WT (interstimulus interval, 20 ms), indicating reduced glutamate release probability. This is fully restored in Dble::R6/2 mice at 12 wk of age. (K) Representative traces of miniature EPSCs (mEPSCs) at 8 wk. R6/2 mice show strongly depressed mEPSC frequency, which is significantly rescued in the Dble::R6/2 mice. (L, M) Average cumulative plot of mEPSC interevent interval (0.1 s bins) (L) or amplitude (1 pA bins) (M); <i>n</i> = 11–12 for all four genotypes. Statistical analysis was performed by (A–H and J) one-way ANOVA with Tukey's multiple comparison test, (I) two-way ANOVA with Bonferroni multiple comparison test, and (L, M) Kolmogorov–Smirnov (KS) test. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.001.</p>", "links"=>[], "tags"=>["improves", "electrophysiological", "msns", "corticostriatal", "synaptic"], "article_id"=>862744, "categories"=>["Uncategorised"], "users"=>["Michal Mielcarek", "Christian Landles", "Andreas Weiss", "Amyaouch Bradaia", "Tamara Seredenina", "Linda Inuabasi", "Georgina F. Osborne", "Kristian Wadel", "Chrystelle Touller", "Rachel Butler", "Janette Robertson", "Sophie A. Franklin", "Donna L. Smith", "Larry Park", "Paul A. Marks", "Erich E. Wanker", "Eric N. Olson", "Ruth Luthi-Carter", "Herman van der Putten", "Vahri Beaumont", "Gillian P. Bates"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001717.g005", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HDAC4_reduction_improves_the_electrophysiological_characteristics_of_MSNs_and_corticostriatal_synaptic_function_/862744", "title"=>"HDAC4 reduction improves the electrophysiological characteristics of MSNs and corticostriatal synaptic function.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-26 03:44:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1296003"], "description"=>"<p>(A) GST pull-down assays revealed that HDAC4 interacts with mutant (53Q) but not WT (20Q) exon 1 HTT. In contrast HDAC5 weakly interacts with both mutant and WT exon 1 HTT. The coomassie stained gel shows the exon 1 HTT GST fusion proteins that were used to pull-down <sup>35</sup>S-methioine labelled recombinant HDAC4 or HDAC5. (B) Western blot probed for HTT (MAB2166 or MW1) after immunoprecipitation with HDAC4 (DM-15) from brain tissue from 8-wk-old WT and <i>Hdh</i>Q150 heterozygous and homozygous mice (representative picture of three independent experiments). (C) Western blot probed for mutant HTT (MW1) after immunoprecipitation with HDAC4 (H-92) from brain tissue from 8-wk-old WT, <i>Hdh</i>Q20, and <i>Hdh</i>Q80 homozygous mice. (D) Western blot probed for mutant HTT (MAB2166 or MW1) after immunoprecipitation with HDAC5 (ab56929) from brain tissue from 8-wk-old WT and <i>Hdh</i>Q80 homozygous mice. (E) Representative immunofluorescence images of cortex from 14-wk-old R6/2 and 23-mo-old <i>Hdh</i>Q150 mice immunostained for mutant HTT (S830) and HDAC4 (CS2072) and counterstained with DAPI. A similar pattern of cytoplasmic co-localisation was also seen in the striatum and hippocampus. Scale bar, 15 µm. IP, immunoprecipitation; ID, immunodetection.</p>", "links"=>[], "tags"=>["interacts", "mutant", "huntingtin", "colocalizes", "cytoplasmic"], "article_id"=>862742, "categories"=>["Uncategorised"], "users"=>["Michal Mielcarek", "Christian Landles", "Andreas Weiss", "Amyaouch Bradaia", "Tamara Seredenina", "Linda Inuabasi", "Georgina F. Osborne", "Kristian Wadel", "Chrystelle Touller", "Rachel Butler", "Janette Robertson", "Sophie A. Franklin", "Donna L. Smith", "Larry Park", "Paul A. Marks", "Erich E. Wanker", "Eric N. Olson", "Ruth Luthi-Carter", "Herman van der Putten", "Vahri Beaumont", "Gillian P. Bates"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001717.g003", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HDAC4_interacts_with_mutant_huntingtin_in_vitro_and_in_vivo_and_colocalizes_with_cytoplasmic_inclusions_/862742", "title"=>"HDAC4 interacts with mutant huntingtin <i>in vitro</i> and <i>in vivo</i> and colocalizes with cytoplasmic inclusions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-11-26 03:44:52"}

PMC Usage Stats | Further Information

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Relative Metric

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