{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:33:26Z","timestamp":1782977606242,"version":"3.54.5"},"reference-count":56,"publisher":"National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,7,8]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Rett syndrome is a devastating neurodevelopmental disorder with diverse symptoms and no available treatment. Previous work from our laboratory has identified deficits in insulin-like growth factor 1 (IGF1) levels in\n                    <jats:italic>Mecp2<\/jats:italic>\n                    mutant mice, and demonstrated correction of symptoms and molecular-signaling alterations with IGF1 treatment. Here, we show that treatment with the adrenergic receptor agonist clenbuterol rescues a microRNA pathway that underlies IGF1 expression, improves survival, and ameliorates diverse phenotypes in\n                    <jats:italic>Mecp2<\/jats:italic>\n                    mutant mice. Life span measurements suggest that cotreatment with clenbuterol and IGF1 may further enhance their therapeutic effects in the mouse model of the disease. We would like to strongly caution, however, against any use of clenbuterol before clinical trials establish its safety and efficacy in Rett syndrome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1309426111","type":"journal-article","created":{"date-parts":[[2014,6,24]],"date-time":"2014-06-24T04:39:14Z","timestamp":1403584754000},"page":"9947-9952","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":64,"title":["\u03b22-Adrenergic receptor agonist ameliorates phenotypes and corrects microRNA-mediated IGF1 deficits in a mouse model of Rett syndrome"],"prefix":"10.1073","volume":"111","author":[{"given":"Nikolaos","family":"Mellios","sequence":"first","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Woodson","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo I.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitendra","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"},{"name":"Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Haggarty","sequence":"additional","affiliation":[{"name":"Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mriganka","family":"Sur","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,6,23]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.10.001"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22124"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(01)00344-8"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/85899"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0b013e32830c3645"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds406"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.02.009"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.011007"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.05.056"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912257106"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3156-09.2009"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4373-05.2005"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198510103131504"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32835f19a7"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn2010"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005595107"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2012.00039"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.12.027"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1311685111"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812394106"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.10.016"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.09.001"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu008"},{"key":"e_1_3_3_25_2","first-page":"679801","article-title":"IGF1 as a potential treatment for Rett syndrome: Safety assessment in six Rett patients","volume":"2012","author":"Pini G","year":"2012","unstructured":"G Pini, et al., IGF1 as a potential treatment for Rett syndrome: Safety assessment in six Rett patients. Autism Res Treat 2012, 679801 (2012).","journal-title":"Autism Res Treat"},{"key":"e_1_3_3_26_2","first-page":"S28.005","article-title":"Initial study of rh-IGF1 (mecasermin [DNA] injection) for treatment of Rett syndrome and development of Rett-specific novel biomarkers of cortical and autonomic function","volume":"78","author":"Ho E","year":"2012","unstructured":"E Ho, et al., Initial study of rh-IGF1 (mecasermin [DNA] injection) for treatment of Rett syndrome and development of Rett-specific novel biomarkers of cortical and autonomic function. Neurology 78, S28.005 (2012).","journal-title":"Neurology"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1311141111"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.06.015"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1101\/lm.030411.113"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.02.003"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000341"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(99)00452-5"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06305.x"},{"key":"e_1_3_3_34_2","first-page":"S43","article-title":"A review of the respiratory disorder in the Rett syndrome","volume":"14","author":"Kerr AM","year":"1992","unstructured":"AM Kerr, A review of the respiratory disorder in the Rett syndrome. Brain Dev 14, S43\u2013S45 (1992).","journal-title":"Brain Dev"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.01.002"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.07.010"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.119966"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(88)80002-9"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.159.1.1609693"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.08.042"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.5.1585"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.4161\/epi.2.4.5212"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.01.036"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.039"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032662"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.08.007"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.03.051"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.2217\/fnl.12.79"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05466.x"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1869-07.2007"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000203157.31924.4a"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02350.x"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181d6b852"},{"key":"e_1_3_3_54_2","first-page":"113ra125","article-title":"Pathogenesis of lethal cardiac arrhythmias in MeCP2 mutant mice: Implication for therapy in Rett syndrome","volume":"3","author":"McCauley MD","year":"2011","unstructured":"MD McCauley, et al., Pathogenesis of lethal cardiac arrhythmias in MeCP2 mutant mice: Implication for therapy in Rett syndrome. Sci TransMed 3, 113ra125 (2011).","journal-title":"Sci TransMed"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1080\/08897077.2013.772083"},{"key":"e_1_3_3_56_2","unstructured":"Committee for the Update on the Guide for the Care and Use of Laboratory Animals (2011) Guide for the Care and Use of Laboratory Animals (The National Academies Press Washington DC) 8th Ed."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1309426111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T21:36:30Z","timestamp":1649799390000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1309426111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,23]]},"references-count":56,"journal-issue":{"issue":"27","published-print":{"date-parts":[[2014,7,8]]}},"alternative-id":["10.1073\/pnas.1309426111"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1309426111","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,23]]},"assertion":[{"value":"2014-06-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}