{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:19:52Z","timestamp":1792059592377,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T00:00:00Z","timestamp":1467849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI2013\/09\u20102, CoEN grant"],"award-info":[{"award-number":["PI2013\/09\u20102, CoEN grant"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007406","name":"Fundaci\u00f3n BBVA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007406","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dendritic alteration of striatal medium spiny neurons is one of the earliest morphological abnormalities in Huntington's disease (HD). The main microtubule\u2010associated protein in dendrites is MAP2. The low\u2010molecular weight isoforms of MAP2 (LMW\u2010MAP2) are the juvenile forms resulting from exclusion of the sequence encoded by exons E7\u2010E9 and are downregulated after the early stages of neuronal development when E7\u2010E9 exon\u2010including high\u2010molecular weight isoforms (HMW\u2010MAP2) are favored. Splicing alteration has recently been proposed to contribute to HD in view of two pathogenic missplicing events resulting in a highly toxic N\u2010terminal version of mutant huntingtin and in a detrimental imbalance in MAP Tau isoforms with three or four tubulin\u2010binding repeats. Both splicing events are postulated targets of the SR splicing factor SRSF6 which has recently been reported to be dramatically altered in HD. SR proteins often regulate functionally related sets of genes and SRSF6 targets are enriched in genes involved in brain organogenesis including several actin\u2010and tubulin\u2010binding proteins. Here we hypothesized that MAP2 might be target of SRSF6 and altered in HD. By SRSF6 knockdown in neuroblastoma cells, we demonstrate that splicing of MAP2 E7\u2010E9 exons is affected by SRSF6. We then show a disbalance in LMW and HMW MAP2 mRNA isoforms in HD striatum in favor of the juvenile LMW forms together with a decrease in total MAP2 mRNA. This is accompanied by a global decrease in total MAP2 protein due to almost total disappearance of HMW\u2010MAP2 isoforms with preservation of LMW\u2010MAP2 isoforms. Accordingly, the predominant dendritic MAP2 staining in striatal neuropil of control subjects is absent in HD cases. In these, MAP2\u2010immunoreactivity is faint and restricted to neuronal cell bodies often showing a sharp boundary at the base of dendrites. Together, our results highlight the importance of splicing alteration in HD and suggest that MAP2 alteration contributes to dendritic atrophy.<\/jats:p>","DOI":"10.1111\/bpa.12387","type":"journal-article","created":{"date-parts":[[2016,4,21]],"date-time":"2016-04-21T08:48:24Z","timestamp":1461228504000},"page":"181-189","source":"Crossref","is-referenced-by-count":36,"title":["MAP2 Splicing is Altered in Huntington's Disease"],"prefix":"10.1111","volume":"27","author":[{"given":"Jorge Rub\u00e9n","family":"Cabrera","sequence":"first","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Cient\u00edficas (CSIC) \u2013 Universidad Aut\u00f3noma de Madrid (UAM) Madrid 28049 Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de Enfermedades Neurodegenerativas (CIBERNED) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 J.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Cient\u00edficas (CSIC) \u2013 Universidad Aut\u00f3noma de Madrid (UAM) Madrid 28049 Spain"},{"name":"Centro de Investigaciones Biom\u00e9dicas en Red de Enfermedades Neurodegenerativas (CIBERNED) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2014.03.011"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.23.10850"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.21.8335"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)01811-0"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-6-1-204"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1998.00044.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3617"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv224"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-12-03877.1991"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/269570"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu456"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201400138"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1624"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2756"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00041444-199903000-00008"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2632"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-3-8"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.27.19261"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.11.030188.000333"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(93)90581-Y"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2009.151"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.113042"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.113014"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(83)90053-9"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.24"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(99)00046-5"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1221891110"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68020862.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl171"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2009.12.006"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv107"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02232.x"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05252.x"}],"container-title":["Brain Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbpa.12387","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbpa.12387","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.12387","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T07:51:31Z","timestamp":1696319491000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bpa.12387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,7]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["10.1111\/bpa.12387"],"URL":"https:\/\/doi.org\/10.1111\/bpa.12387","archive":["Portico"],"relation":{},"ISSN":["1015-6305","1750-3639"],"issn-type":[{"value":"1015-6305","type":"print"},{"value":"1750-3639","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,7]]}}}