{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:28:26Z","timestamp":1791106106595,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,11,20]],"date-time":"2007-11-20T00:00:00Z","timestamp":1195516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2008,4]]},"abstract":"<jats:p>\n                    Huntington's disease (HD) is a neurodegenerative disorder due to an abnormal polyglutamine expansion in the N\u2010terminal region of huntingtin protein (Exp\u2010Htt). This expansion causes protein aggregation and neuronal dysfunction and death. Transcriptional dysregulation due to Exp\u2010Htt participates in neuronal death in HD. Here, using the R6\/2 transgenic mouse model of HD, we identified a new molecular alteration that could account for gene dysregulation in these mice. Despite a nuclear activation of the mitogen\u2010activated protein kinase\/extracellular regulated kinase (ERK) along with Elk\u20101 and cAMP responsive element binding, two transcription factors involved in c\u2010Fos transcription, we failed to detect any histone H3 phosphorylation, which is expected after nuclear ERK activation. Accordingly, we found in the striatum of these mice a deficiency of mitogen\u2010 and stress\u2010activated kinase\u20101 (MSK\u20101), a kinase downstream ERK, critically involved in H3 phosphorylation and c\u2010Fos induction. We extended this observation to Exp\u2010Htt\u2010expressing striatal neurons and\n                    <jats:italic>postmortem<\/jats:italic>\n                    brains of HD patients.\n                    <jats:italic>In vitro,<\/jats:italic>\n                    knocking out MSK\u20101 expression potentiated Exp\u2010Htt\u2010induced striatal death. Its overexpression induced H3 phosphorylation and c\u2010Fos expression and totally protected against striatal neurodegeneration induced by Exp\u2010Htt. We propose that MSK\u20101 deficiency is involved in transcriptional dysregulation and striatal degeneration. Restoration of its expression and activity may be a new therapeutic target in HD. Roze E., Betuing, S., Deyts, C., Marcon, E., Brami\u2010Cherrier, K., Pages, C., Humbert, S., M\u00e9rienne, K., Caboche J. Mitogen\u2010 and stress\u2010activated protein kinase\u20101 deficiency is involved in expanded\u2010hunting\u2010tin\u2010induced transcriptional dysregulation and striatal death. FASEB J. 22, 1083\u20131093 (2008)\n                  <\/jats:p>","DOI":"10.1096\/fj.07-9814","type":"journal-article","created":{"date-parts":[[2007,11,20]],"date-time":"2007-11-20T20:44:59Z","timestamp":1195591499000},"page":"1083-1093","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Mitogen\u2010 and stress\u2010activated protein kinase\u20101 deficiency is involved in expanded\u2010huntingtin\u2010induced transcriptional dysregulation and striatal death"],"prefix":"10.1096","volume":"22","author":[{"given":"Emmanuel","family":"Roze","sequence":"first","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie\u2010Paris 6, CNRS, UMR 7102 Paris France"},{"name":"Service de Neurologie H\u00f4pital Saint\u2010Antoine Assitance Publique\u2010H\u00f4pitaux de Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Bettuing","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie\u2010Paris 6, CNRS, UMR 7102 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Deyts","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie\u2010Paris 6, CNRS, UMR 7102 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Marcon","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie\u2010Paris 6, CNRS, UMR 7102 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Brami\u2010Cherrier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie\u2010Paris 6, INSERM, UMRS 839 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Pag\u00e8s","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre et Marie Curie\u2010Paris 6, CNRS, UMR 7102 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Humbert","sequence":"additional","affiliation":[{"name":"Institut Curie, CNRS, UMR 146 Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"M\u00e9rienne","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire D\u00e9partement de pathologie mol\u00e9culaire; 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