{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:19:20Z","timestamp":1791314360784,"version":"4.3.1"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2010,10,15]],"date-time":"2010-10-15T00:00:00Z","timestamp":1287100800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0013417","type":"journal-article","created":{"date-parts":[[2010,10,15]],"date-time":"2010-10-15T19:35:38Z","timestamp":1287171338000},"page":"e13417","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":171,"title":["Inhibition of the Striatal Specific Phosphodiesterase PDE10A Ameliorates Striatal and Cortical Pathology in R6\/2 Mouse Model of Huntington's Disease"],"prefix":"10.1371","volume":"5","author":[{"given":"Carmela","family":"Giamp\u00e0","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daunia","family":"Laurenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serenella","family":"Anzilotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Bernardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank S.","family":"Menniti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Romana","family":"Fusco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2010,10,15]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S0140-6736(07)60111-1","article-title":"Huntington&apos;s disease.","volume":"369","author":"FO Walker","year":"2007","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat is expanded and unstable on Huntington&apos;s disease chromosomes.","volume":"72","year":"1993","journal-title":"Cell"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0092-8674(00)81369-0","article-title":"Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice.","volume":"87","author":"L Mangiarini","year":"1996","journal-title":"Cell"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/ng0893-398","article-title":"The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington&apos;s disease.","volume":"4","author":"SE Andrew","year":"1993","journal-title":"Nature Genetics"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1097\/00005072-198511000-00003","article-title":"Neuropathological classification of Huntington&apos;s disease.","volume":"44","author":"JP Vonsattel","year":"1985","journal-title":"J Neuropathol Exp Neurol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/00005072-198809000-00003","article-title":"Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington&apos;s disease.","volume":"47","author":"SM de la Monte","year":"1988","journal-title":"J Neuropathol Exp Neurol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","article-title":"Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain.","volume":"277","author":"M DiFiglia","year":"1997","journal-title":"Science"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1016\/S0140-6736(03)13304-1","article-title":"Huntingtin aggregation and toxicity in Huntington&apos;s disease.","volume":"361","author":"G Bates","year":"2003","journal-title":"Lancet"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1002\/1531-8249(199912)46:6<842::AID-ANA6>3.0.CO;2-O","article-title":"Huntington aggregates may not predict neuronal death in Huntington&apos;s disease.","volume":"46","author":"S Kuemmerle","year":"1999","journal-title":"Annals of Neurology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1517\/13543784.16.12.1933","article-title":"Huntington&apos;s disease: progress and potential in the field.","volume":"16","author":"EC Stack","year":"2007","journal-title":"Expert Opin Investig Drugs"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1042\/BJ20071619","article-title":"Huntington&apos;s disease: from pathology and genetics to potential therapies.","volume":"412","author":"S Imarisio","year":"2008","journal-title":"Biochemical Journal"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/hmg\/ddg046","article-title":"Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington&apos;s disease knock-in mice.","volume":"12","author":"S Gines","year":"2003","journal-title":"Human Molecular Genetics"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0168-9525(03)00074-X","article-title":"Transcriptional abnormalities in Huntington disease.","volume":"19","author":"KL Sugars","year":"2003","journal-title":"Trends in Genetics"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"4988","DOI":"10.1074\/jbc.M310226200","article-title":"Decreased cAMP response element-mediated transcription, an early event in exon 1 and full-length cell models of Huntington&apos;s disease that contributes to polyglutamine pathogenesis.","volume":"279","author":"KL Sugars","year":"2004","journal-title":"J Biol Chem"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/hmg\/ddg002","article-title":"Cell death triggered by polyglutamine-expanded huntingtin in a neuronal cell line is associated with degradation of CREB-binding protein.","volume":"12","author":"H Jiang","year":"2003","journal-title":"Human Molecular Genetics"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1126\/science.1056784","article-title":"Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity.","volume":"291","author":"FC Nucifora Jr","year":"2001","journal-title":"Science"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"6763","DOI":"10.1073\/pnas.100110097","article-title":"The Huntington&apos;s disease protein interacts with p53 and CREB-binding protein and represses transcription.","volume":"97","author":"JS Steffan","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1038\/35099568","article-title":"Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila.","volume":"413","author":"JS Steffan","year":"2001","journal-title":"Nature"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1093\/hmg\/9.9.1259","article-title":"Decreased expression of striatal signaling genes in a mouse model of Huntington&apos;s disease.","volume":"9","author":"R Luthi-Carter","year":"2000","journal-title":"Human Molecular Genetics"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1093\/hmg\/10.17.1829","article-title":"Polyglutamine expansions cause decreased CRE-mediated transcription and early gene expression changes prior to cell death in an inducible cell model of Huntington&apos;s disease.","volume":"10","author":"A Wyttenbach","year":"2001","journal-title":"Human Molecular Genetics"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj20021698","article-title":"PDE4 cAMP phosphodiesterases: modular enzymes that orchestrate signalling cross-talk, desensitization and compartmentalization.","volume":"370","author":"MD Houslay","year":"2003","journal-title":"Biochem J"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1146\/annurev.biochem.76.060305.150444","article-title":"Biochemistry and Physiology of Cyclic Nucleotide Phosphodiesterases: Essential Components in Cyclic Nucleotide Signaling.","volume":"76","author":"M Conti","year":"2007","journal-title":"Annual Review of Biochemistry"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nrd2058","article-title":"Phosphodiesterases in the CNS: targets for drug development.","volume":"5","author":"FS Menniti","year":"2006","journal-title":"Nat Rev Drug Discov"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1042\/bj3470571","article-title":"Action of rolipram on specific PDE4 cAMP phosphodiesterase isoforms and on the phosphorylation of cAMP-response-element-binding protein (CREB) and p38 mitogen-activated protein (MAP) kinase in U937 monocytic cells.","volume":"347","author":"SJ MacKenzie","year":"2000","journal-title":"Biochemical Journal"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.tins.2005.06.005","article-title":"The many faces of CREB.","volume":"28","author":"WA Carlezon Jr","year":"2005","journal-title":"Trends Neurosci"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.nbd.2006.09.006","article-title":"Beneficial effects of rolipram in a quinolinic acid model of striatal excitotoxicity.","volume":"25","author":"Z DeMarch","year":"2007","journal-title":"Neurobiology of Disease"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.nbd.2008.02.010","article-title":"Beneficial effects of rolipram in the R6\/2 mouse model of Huntington&apos;s disease.","volume":"30","author":"Z DeMarch","year":"2008","journal-title":"Neurobiology of Disease"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1369\/jhc.6A6930.2006","article-title":"Immunohistochemical Localization of Phosphodiesterase 10A in Multiple Mammalian Species.","volume":"54","author":"TM Coskran","year":"2006","journal-title":"J Histochem Cytochem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0006-8993(03)02754-9","article-title":"Immunohistochemical localization of PDE10A in the rat brain.","volume":"985","author":"TF Seeger","year":"2003","journal-title":"Brain Research"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.neuroscience.2005.12.042","article-title":"Cellular and subcellular localization of PDE10A, a striatum-enriched phosphodiesterase.","volume":"139","author":"Z Xie","year":"2006","journal-title":"Neuroscience"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.neuropharm.2006.04.013","article-title":"Inhibition of the striatum-enriched phosphodiesterase PDE10A: A novel approach to the treatment of psychosis.","volume":"51","author":"JA Siuciak","year":"2006","journal-title":"Neuropharmacology"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.neuropharm.2006.01.012","article-title":"Genetic deletion of the striatum-enriched phosphodiesterase PDE10A: Evidence for altered striatal function.","volume":"51","author":"JA Siuciak","year":"2006","journal-title":"Neuropharmacology"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1124\/jpet.107.132910","article-title":"Preclinical Characterization of Selective Phosphodiesterase 10A Inhibitors: A New Therapeutic Approach to the Treatment of Schizophrenia.","volume":"325","author":"CJ Schmidt","year":"2008","journal-title":"J Pharmacol Exp Ther"},{"key":"ref34","article-title":"Phosphodiesterase 10 inhibition reduces striatal excitotoxicity in the quinolinic acid model of Huntington&apos;s disease.","author":"C Giamp\u00e0","year":"2009","journal-title":"Neurobiology of Disease In press"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0006-8993(02)04275-0","article-title":"Overexpression of heat shock protein 70 in R6\/2 Huntington&apos;s disease mice has only modest effects on disease progression.","volume":"970","author":"O Hansson","year":"2003","journal-title":"Brain Research"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1602\/neurorx.1.3.298","article-title":"Translating therapies for Huntington&apos;s disease from genetic animal models to clinical trials.","volume":"1","author":"SM Hersch","year":"2004","journal-title":"NeuroRX"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.neulet.2006.10.039","article-title":"Metformin therapy in a transgenic mouse model of Huntington&apos;s disease.","volume":"411","author":"TC Ma","year":"2007","journal-title":"Neuroscience Letters"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/ana.10094","article-title":"Environmental enrichment slows disease progression in R6\/2 Huntington&apos;s disease mice.","volume":"51","author":"E Hockly","year":"2002","journal-title":"Annals of Neurology"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.bbadis.2005.11.002","article-title":"Combination therapy using minocycline and coenzyme Q10 in R6\/2 transgenic Huntington&apos;s disease mice.","volume":"1762","author":"EC Stack","year":"2006","journal-title":"Biochim Biophys Acta"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1523\/JNEUROSCI.19-07-02522.1999","article-title":"Nuclear and neuropil aggregates in Huntington&apos;s disease: relationship to neuropathology.","volume":"19","author":"CA Gutekunst","year":"1999","journal-title":"Journal of Neuroscience"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1471-4159.2007.05152.x","article-title":"Increased social interaction in mice deficient of the striatal medium spiny neuron-specific phosphodiesterase 10A2.","volume":"105","author":"H Sano","year":"2008","journal-title":"Journal of Neurochemistry"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.neuropharm.2009.09.008","article-title":"Alterations in gene regulation following inhibition of the striatum-enriched phosphodiesterase, PDE10A.","volume":"58","author":"CA Strick","year":"2010","journal-title":"Neuropharmacology"},{"key":"ref43","article-title":"Chronic suppression of PDE10A alters striatal expression of genes responsible for neurotransmitter synthesis, neurotransmission and signaling pathways implicated in Huntington&apos;s Disease.","author":"RJ Kleiman","year":"2010","journal-title":"Journal of Pharmacology and Experimental Theraputics. In press"},{"key":"ref44","first-page":"431","article-title":"Analysis of neurotransmitter metabolites and adenosine 3\u2032,5\u2032-monophosphate in the CSF of patients with extrapyramidal motor disorders.","volume":"40","author":"H Cramer","year":"1984","journal-title":"Adv Neurol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1750-3639.2007.00111.x","article-title":"Systematic assessment of BDNF and its receptor levels in human cortices affected by Huntington&apos;s disease.","volume":"18","author":"C Zuccato","year":"2008","journal-title":"Brain Pathol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1126\/science.1059581","article-title":"Loss of huntingtin-mediated BDNF gene transcription in Huntington&apos;s disease.","volume":"293","author":"C Zuccato","year":"2001","journal-title":"Science"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1471-4159.2007.05137.x","article-title":"Brain-derived neurotrophic factor over-expression in the forebrain ameliorates Huntington&apos;s disease phenotypes in mice.","volume":"105","author":"K Gharami","year":"2008","journal-title":"Journal of Neurochemistry"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.pneurobio.2007.01.003","article-title":"Role of brain-derived neurotrophic factor in Huntington&apos;s disease.","volume":"81","author":"C Zuccato","year":"2007","journal-title":"Progress in Neurobiology"},{"key":"ref49","first-page":"458","article-title":"PDE10A Inhibitors: An Assessment of the Current CNS Drug Discovery Landscape.","volume":"12","author":"TA Chappie","year":"2009","journal-title":"Current Opinion in Investigational Drugs"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1517\/13543770903431050","article-title":"Patented PDE10A inhibitors: novel compounds since 2007.","volume":"19","author":"J Kehler","year":"2009","journal-title":"Expert Opin Ther Pat"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"7946","DOI":"10.1021\/jm900521k","article-title":"Discovery of a Novel Class of Phosphodiesterase 10A Inhibitors and Identification of Clinical Candidate 2-[4-(1-Methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the Treatment of Schizophrenia.","volume":"52","author":"PR Verhoest","year":"2009","journal-title":"J Med Chem"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1523\/JNEUROSCI.19-04-01189.1999","article-title":"Cellular localization of huntingtin in striatal and cortical neurons in rats: lack of correlation with neuronal vulnerability in Huntington&apos;s disease.","volume":"19","author":"FR Fusco","year":"1999","journal-title":"Journal of Neuroscience"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1460-9568.2005.04545.x","article-title":"Striatal modulation of cAMP-response-element-binding protein CREB. after excitotoxic lesions, implications with neuronal vulnerability in Huntington&apos;s disease.","volume":"23","author":"C Giampa","year":"2006","journal-title":"Eur J Neurosci"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1046\/j.1460-9568.2003.02844.x","article-title":"Co-localization of brain-derived neurotrophic factor (BDNF) and wild-type huntingtin in normal and quinolinic acid-lesioned rat brain.","volume":"18","author":"FR Fusco","year":"2003","journal-title":"Eur J Neurosci"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.expneurol.2008.10.008","article-title":"Implication of the JNK pathway in a rat model of Huntington&apos;s disease.","volume":"215","author":"V Perrin","year":"2009","journal-title":"Exp Neurol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1080\/01621459.1958.10501452","article-title":"Nonparametric estimation from incomplete observations.","volume":"53","author":"EL Kaplan","year":"1958","journal-title":"Journal of the American Statistical Association"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0013417","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T17:40:05Z","timestamp":1589046005000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0013417"}},"subtitle":[],"editor":[{"given":"David C.","family":"Rubinsztein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2010,10,15]]},"references-count":56,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2010,10,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0013417","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,10,15]]}}}