{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:19:38Z","timestamp":1792059578451,"version":"4.4.0"},"reference-count":61,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,11,27]],"date-time":"2016-11-27T00:00:00Z","timestamp":1480204800000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas","award":["CiberNed-PI2015-2\/06-3"],"award-info":[{"award-number":["CiberNed-PI2015-2\/06-3"]}]},{"name":"Spanish Ministery of Economy and Competitiveness","award":["MINECO, SAF2015-65371-R"],"award-info":[{"award-number":["MINECO, SAF2015-65371-R"]}]},{"name":"Fundaci\u00f3n BBVA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Huntington's disease (HD) is caused by a CAG\u2010repeat encoding a polyglutamine (polyQ) tract in the huntingtin protein. There is plenty of evidence of polyQ\u2010driven toxicity. However, CAG repeat RNA\u2010driven alteration of splicing has recently been proposed in analogy to CUG\u2010repeat diseases. Here we review the reported alteration of the CAG\u2010repeat associated splicing factor SRSF6 in brains of HD patients and mouse models and how this correlates with altered splicing of, at least, two microtubule\u2010associated proteins in HD, namely MAPT (tau) and MAP2. Regarding tau, altered splicing of exon 10 has been reported, along with increased levels and 4R\/3R\u2010tau ratio and detection of tau in a new nuclear rod\u2010shaped histopathological hallmark termed tau nuclear rod (TNR) or tau nuclear indentation (TNI). These findings, together with an attenuation of HD phenotype in R6\/1 mice with tau deficiency and subsequent studies showing increased phosphorylation in mouse models and increased levels in CSF of patients, has led to proposing HD as a tauopathy. Regarding MAP2, an increase in its juvenile form and a decrease in total MAP2 together with redistribution from dendrites to soma is observed in HD patients, which may contribute to the dendritic atrophy in HD. Furthermore, MAP2 positive structures filling nuclear indentations have occasionally been found and co\u2010localized with tau. Therefore, altered MAP function with imbalance in tau\/MAP2 content could contribute to HD striatal atrophy and dysfunction. Besides, TNIs might be indicative of such MAP abnormalities. TNIs are also found in early pathology Alzheimer's disease and in tauopathy mice over\u2010expressing mutant 4R\u2010tau. This indicates that tau alteration is sufficient for TNI detection, which becomes a marker of increased total tau and\/or altered 4R\/3R\u2010tau ratio and reporter of pathology\u2010associated nuclear indentations. Altogether, these recent studies suggest that correcting the SRSF6\u2010driven missplicing and\/or microtubule\u2010associated imbalance might be of therapeutic value in HD.<\/jats:p>","DOI":"10.1111\/bpa.12430","type":"journal-article","created":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T12:32:38Z","timestamp":1471350758000},"page":"772-778","source":"Crossref","is-referenced-by-count":43,"title":["Faulty splicing and cytoskeleton abnormalities in\n                    <scp>H<\/scp>\n                    untington's disease"],"prefix":"10.1111","volume":"26","author":[{"given":"Marta","family":"Fern\u00e1ndez\u2010Nogales","sequence":"first","affiliation":[{"name":"Center for Molecular Biology \u201cSevero Ochoa\u201d (CBMSO) CSIC\/UAM Madrid 28049 Spain"},{"name":"Instituto de Salud Carlos III Networking Research Center on Neurodegenerative Diseases (CIBERNED)  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Santos\u2010Galindo","sequence":"additional","affiliation":[{"name":"Center for Molecular Biology \u201cSevero Ochoa\u201d (CBMSO) CSIC\/UAM Madrid 28049 Spain"},{"name":"Instituto de Salud Carlos III Networking Research Center on Neurodegenerative Diseases (CIBERNED)  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00f3 H.","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Center for Molecular Biology \u201cSevero Ochoa\u201d (CBMSO) CSIC\/UAM Madrid 28049 Spain"},{"name":"Instituto de Salud Carlos III Networking Research Center on Neurodegenerative Diseases (CIBERNED)  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge R.","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Dartmouth College Lebanon NH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 J.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Center for Molecular Biology \u201cSevero Ochoa\u201d (CBMSO) CSIC\/UAM Madrid 28049 Spain"},{"name":"Instituto de Salud Carlos III Networking Research Center on Neurodegenerative Diseases (CIBERNED)  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,11,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2014.03.011"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00024.2003"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.101.4.1371"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu421"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00691525"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12387"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2014.03.002"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2011.06.010"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1177452"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.17.030194.001411"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-6-1-204"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-37-11653.2003"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.7.1169"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.1998.00044.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3617"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv224"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12407"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.11-12-03877.1991"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3778"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.740490.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1691"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.06.018"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/269570"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.23.1.39"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww021"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu456"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)91524-0"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00194305"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. 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