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Currently, disease\u2010modifying therapy is not available for <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>, and only symptomatic drugs are administered for the management of symptoms. In the last few years, preclinical and clinical studies have indicated that pharmacological strategies aimed at inhibiting cyclic nucleotide phosphodiesterase (<jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>s) may develop into a novel therapeutic approach in neurodegenerative disorders. <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>s are a family of enzymes that hydrolyze cyclic nucleotides into monophosphate isoforms. Cyclic nucleotides are second messengers that transduce the signal of hormones and neurotransmitters in many physiological processes, such as protein kinase cascades and synaptic transmission. An alteration in their balance results in the dysregulation of different biological mechanisms (transcriptional dysregulation, immune cell activation, inflammatory mechanisms, and regeneration) that are involved in neurological diseases. In this review, we discuss the action of phosphodiesterase inhibitors and their role as therapeutic agents in <jats:styled-content style=\"fixed-case\">HD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cns.12834","type":"journal-article","created":{"date-parts":[[2018,3,3]],"date-time":"2018-03-03T18:56:35Z","timestamp":1520103395000},"page":"319-328","source":"Crossref","is-referenced-by-count":40,"title":["Inhibition of phosphodiesterases as a strategy to achieve neuroprotection in Huntington's disease"],"prefix":"10.1111","volume":"24","author":[{"given":"Antonella","family":"Cardinale","sequence":"first","affiliation":[{"name":"Laboratory of Neuroanatomy Santa Lucia Foundation IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2226-523X","authenticated-orcid":false,"given":"Francesca R.","family":"Fusco","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroanatomy Santa Lucia Foundation IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(95)93943-R"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90585-E"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199805000-00001"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2003.07.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399403006549"},{"key":"e_1_2_8_7_1","first-page":"506","article-title":"Huntington disease: genetics and epidemiology","volume":"36","author":"Conneally PM","year":"1984","journal-title":"Am J Hum Genet"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60111-1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-198511000-00003"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.15.5733"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0306-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)00427-7"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3233\/JHD-2012-120009","article-title":"Functional differences between direct and indirect striatal output pathways in Huntington's disease","volume":"1","author":"Galvan L","year":"2012","journal-title":"J Huntingtons Dis"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06310.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.100110097"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/35099568"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1056784"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.07.014"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg002"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2007.01.003"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4278-06.2007"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059581"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02844.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1806"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02237-X"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05137.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1637-10.2010"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064037"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.3.5"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.06.038"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.294.5544.1024"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01249105"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-5994.1995.tb02886.x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1081\/RRS-200029981"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2004.06.006"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071550"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404706200"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01297.x"},{"key":"e_1_2_8_39_1","first-page":"2859","article-title":"Cyclic 3\u2032,5\u2032\u2010nucleotide phosphodiesterase. 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