{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:10:50Z","timestamp":1780333850340,"version":"3.54.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T00:00:00Z","timestamp":1451260800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neuropsychopharmacol"],"published-print":{"date-parts":[[2016,7]]},"DOI":"10.1038\/npp.2015.369","type":"journal-article","created":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T12:00:58Z","timestamp":1451304058000},"page":"1991-2000","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Targeting Translation Control with p70 S6 Kinase 1 Inhibitors to Reverse Phenotypes in Fragile X Syndrome Mice"],"prefix":"10.1038","volume":"41","author":[{"given":"Aditi","family":"Bhattacharya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Mamcarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Mullins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Choudhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G","family":"Boyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4637-8992","authenticated-orcid":false,"given":"Daniel G","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Klann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,12,28]]},"reference":[{"key":"BFnpp2015369_CR1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders, 5th edn. Americal Psychiatric Publishing: Arlington, VA.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"BFnpp2015369_CR2","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.neuron.2012.07.022","volume":"76","author":"A Bhattacharya","year":"2012","unstructured":"Bhattacharya A, Kaphzan H, Alvarez-Dieppa AC, Murphy JP, Pierre P, Klann E (2012). Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. Neuron 76: 325\u2013337.","journal-title":"Neuron"},{"key":"BFnpp2015369_CR3","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.neuropharm.2015.07.017","volume":"100","author":"H Bowling","year":"2016","unstructured":"Bowling H, Bhattacharya A, Zhang G, Lebowitz JZ, Alam D, Smith P et al (2016). BONLAC: a combinatorial proteomic technique to measure stimulus-induced translational profiles in brain slices. Neuropharmacology 100: 76\u201389.","journal-title":"Neuropharmacology"},{"key":"BFnpp2015369_CR4","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.neuron.2008.10.055","volume":"61","author":"M Costa-Mattioli","year":"2009","unstructured":"Costa-Mattioli M, Sossin WS, Klann E, Sonenberg N (2009). Translational control of long-lasting synaptic plasticity and memory. Neuron 61: 10\u201326.","journal-title":"Neuron"},{"key":"BFnpp2015369_CR5","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.18632\/oncotarget.1255","volume":"4","author":"S Couty","year":"2013","unstructured":"Couty S, Westwood IM, Kalusa A, Cano C, Travers J, Boxall K et al (2013). The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design. Oncotarget 4: 1647\u20131661.","journal-title":"Oncotarget"},{"key":"BFnpp2015369_CR6","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1038\/nn.3379","volume":"16","author":"JC Darnell","year":"2013","unstructured":"Darnell JC, Klann E (2013). The translation of translational control by FMRP: therapeutic targets for FXS. Nat Neurosci 16: 1530\u20131536.","journal-title":"Nat Neurosci"},{"key":"BFnpp2015369_CR7","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1111\/bjh.12945","volume":"166","author":"TA Eyre","year":"2014","unstructured":"Eyre TA, Collins GP, Goldstone AH, Cwynarski K (2014). Time now to TORC the TORC? New developments in mTOR pathway inhibition in lymphoid malignancies. Br J Haematol 166: 336\u2013351.","journal-title":"Br J Haematol"},{"key":"BFnpp2015369_CR8","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1016\/j.celrep.2014.10.064","volume":"9","author":"CG Gkogkas","year":"2014","unstructured":"Gkogkas CG, Khoutorsky A, Cao R, Jafarnejad SM, Prager-Khoutorsky M, Giannakas N et al (2014). Pharmacogenetic inhibition of eIF4E-dependent Mmp9 mRNA translation reverses fragile X syndrome-like phenotypes. Cell Rep 9: 1742\u20131755.","journal-title":"Cell Rep"},{"key":"BFnpp2015369_CR9","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.celrep.2015.03.060","volume":"11","author":"C Gross","year":"2015","unstructured":"Gross C, Chang CW, Kelly SM, Bhattacharya A, McBride SM, Danielson SW et al (2015a). Increased expression of the PI3K enhancer PIKE mediates deficits in synaptic plasticity and behavior in fragile X syndreome. Cell Rep 11: 727\u2013736.","journal-title":"Cell Rep"},{"key":"BFnpp2015369_CR10","doi-asserted-by":"publisher","first-page":"10624","DOI":"10.1523\/JNEUROSCI.0402-10.2010","volume":"30","author":"C Gross","year":"2010","unstructured":"Gross C, Nakamoto M, Yao X, Chan CB, Yim SY, Ye K et al (2010). Excess phosphoinositide 3-kinase subunit synthesis and activity as a novel therapeutic target in fragile X syndrome. J Neurosci 30: 10624\u201310638.","journal-title":"J Neurosci"},{"key":"BFnpp2015369_CR11","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.celrep.2015.03.065","volume":"11","author":"C Gross","year":"2015","unstructured":"Gross C, Raj N, Molinaro G, Allen AG, Whyte AJ, Gibson JR et al (2015b). Selective role of the catalytic PI3K subunit p110\u03b2 in impaired higher order cognition in fragile X syndrome. Cell Rep 11: 681\u2013688.","journal-title":"Cell Rep"},{"key":"BFnpp2015369_CR12","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1097\/00004703-198306000-00009","volume":"4","author":"RJ Hagerman","year":"1983","unstructured":"Hagerman RJ, McBogg P, Hagerman PJ (1983). The fragile X syndrome: history, diagnosis, and treatment. J Dev Behav Pediatr 4: 122\u2013130.","journal-title":"J Dev Behav Pediatr"},{"key":"BFnpp2015369_CR13","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.tins.2009.11.003","volume":"33","author":"CA Hoeffer","year":"2010","unstructured":"Hoeffer CA, Klann E (2010). mTOR signaling: at the crossroads of plasticity, memory and disease. Trends Neurosci 33: 67\u201375.","journal-title":"Trends Neurosci"},{"key":"BFnpp2015369_CR14","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1111\/j.1601-183X.2012.00768.x","volume":"11","author":"CA Hoeffer","year":"2012","unstructured":"Hoeffer CA, Sanchez E, Hagerman RJ, Mu Y, Nguyen DV, Wong H et al (2012). Altered mTOR signaling and enhanced CYFIP2 expression levels in subjects with fragile X syndrome. Genes Brain Behav 11: 332\u2013341.","journal-title":"Genes Brain Behav"},{"key":"BFnpp2015369_CR15","doi-asserted-by":"publisher","first-page":"3159","DOI":"10.4161\/cc.21194","volume":"11","author":"MK Holz","year":"2012","unstructured":"Holz MK (2012). The role of S6K1 in ER-positive breast cancer. Cell Cycle 11: 3159\u20133165.","journal-title":"Cell Cycle"},{"key":"BFnpp2015369_CR16","doi-asserted-by":"publisher","first-page":"9034","DOI":"10.1523\/JNEUROSCI.0878-14.2014","volume":"34","author":"TN Huynh","year":"2014","unstructured":"Huynh TN, Santini E, Klann E (2014). Requirement of mammalian target of rapamycin complex 1 downstream effectors in cued fear memory reconsolidation and its persistence. J Neurosci 34: 9034\u20139039.","journal-title":"J Neurosci"},{"key":"BFnpp2015369_CR17","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1002\/humu.22699","volume":"35","author":"D Kumari","year":"2014","unstructured":"Kumari D, Bhattacharya A, Nadel J, Moulton K, Zeak NM, Glicksman A et al (2014). Identification of fragile X syndrome-specific molecular markers in human fibroblasts: a useful model to test the efficacy of therapeutic drugs. Hum Mutat 35: 1485\u20131494.","journal-title":"Hum Mutat"},{"key":"BFnpp2015369_CR18","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.neuron.2014.09.034","volume":"84","author":"JO Lipton","year":"2014","unstructured":"Lipton JO, Sahin M (2014). The neurology of mTOR. Neuron 84: 275\u2013291.","journal-title":"Neuron"},{"key":"BFnpp2015369_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/BJ20110892","volume":"441","author":"B Magnuson","year":"2012","unstructured":"Magnuson B, Ekim B, Fingar DC (2012). Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. Biochem J 441: 1\u201321.","journal-title":"Biochem J"},{"key":"BFnpp2015369_CR20","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.neuron.2012.03.009","volume":"74","author":"A Michalon","year":"2012","unstructured":"Michalon A, Sidorov M, Ballard TM, Ozmen L, Spooren W, Wettstein JG et al (2012). Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron 74: 49\u201356.","journal-title":"Neuron"},{"key":"BFnpp2015369_CR21","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s10969-014-9188-8","volume":"15","author":"H Niwa","year":"2014","unstructured":"Niwa H, Mikuni J, Sasaki S, Tomabechi Y, Honda K, Ikeda M et al (2014). Crystal structures of the S6K1 kinase domain in complexes with inhibitors. J Struct Funct Genomics 15: 153\u2013164.","journal-title":"J Struct Funct Genomics"},{"key":"BFnpp2015369_CR22","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.neuron.2012.01.034","volume":"77","author":"EK Osterweil","year":"2013","unstructured":"Osterweil EK, Chuang SC, Chubykin AA, Sidorov M, Bianchi R, Wong RK et al (2013). Lovastatin corrects excess protein synthesis and prevents epileptogenesis in a mouse model of fragile X syndrome. Neuron 77: 243\u2013250.","journal-title":"Neuron"},{"key":"BFnpp2015369_CR23","doi-asserted-by":"publisher","first-page":"15616","DOI":"10.1523\/JNEUROSCI.3888-10.2010","volume":"30","author":"EK Osterweil","year":"2010","unstructured":"Osterweil EK, Krueger DD, Reinhold K, Bear MF (2010). Hypersensitivity to mGluR5 and ERK1\/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome. J Neurosci 30: 15616\u201315627.","journal-title":"J Neurosci"},{"key":"BFnpp2015369_CR24","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1042\/BJ20101024","volume":"431","author":"LR Pearce","year":"2010","unstructured":"Pearce LR, Alton GR, Richter DT, Kath JC, Lingardo L, Chapman J et al (2010). Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). Biochem J 431: 245\u2013255.","journal-title":"Biochem J"},{"key":"BFnpp2015369_CR25","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1007\/s00213-012-2947-y","volume":"231","author":"AS Pop","year":"2013","unstructured":"Pop AS, Levenga J, de Esch CE, Buijsen RA, Nieuwenhuizen IM, Li T (2013). Rescue of dendritic spine phenotype in Fmr1 KO mice with the mGluR5 antagonist AFQ056\/mavoglurant. Psychopharmacology (Berl) 231: 1227\u20131235.","journal-title":"Psychopharmacology (Berl)"},{"key":"BFnpp2015369_CR26","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1038\/nrn4001","volume":"16","author":"JD Richter","year":"2015","unstructured":"Richter JD, Bassell GJ, Klann E (2015). Dysregulation and restoration of translational homeostasis in fragile X syndrome. Nat Rev Neurosci 16: 595\u2013605.","journal-title":"Nat Rev Neurosci"},{"key":"BFnpp2015369_CR27","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1146\/annurev-pathol-011811-132457","volume":"7","author":"MR Santoro","year":"2012","unstructured":"Santoro MR, Bray SM, Warren ST (2012). Molecular mechanisms of fragile X syndrome: a twenty-year perspective. Annu Rev Pathol 7: 219\u2013245.","journal-title":"Annu Rev Pathol"},{"key":"BFnpp2015369_CR28","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1126\/science.1177221","volume":"326","author":"C Selman","year":"2009","unstructured":"Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI et al (2009). Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326: 140\u2013144.","journal-title":"Science"},{"key":"BFnpp2015369_CR29","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1523\/JNEUROSCI.3696-09.2010","volume":"30","author":"A Sharma","year":"2010","unstructured":"Sharma A, Hoeffer CA, Takayasu Y, Miyawaki T, McBride SM, Klann E et al (2010). Dysregulation of mTOR signaling in fragile X syndrome. J Neurosci 30: 694\u2013702.","journal-title":"J Neurosci"},{"key":"BFnpp2015369_CR30","doi-asserted-by":"publisher","first-page":"6649","DOI":"10.1093\/emboj\/17.22.6649","volume":"17","author":"H Shima","year":"1998","unstructured":"Shima H, Pende M, Chen Y, Fumagalli S, Thomas G, Kozma SC (1998). Disruption of the p70(s6k)\/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase. EMBO J 17: 6649\u20136659.","journal-title":"EMBO J"},{"key":"BFnpp2015369_CR31","doi-asserted-by":"publisher","first-page":"9867","DOI":"10.1523\/JNEUROSCI.1162-14.2014","volume":"34","author":"H Sidhu","year":"2014","unstructured":"Sidhu H, Dansie LE, Hickmott PW, Ethell DW, Ethell IM (2014). Genetic removal of matrix metalloproteinase 9 rescues the symptoms of fragile X syndrome in a mouse model. J Neurosci 34: 9867\u20139879.","journal-title":"J Neurosci"},{"key":"BFnpp2015369_CR32","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/j.ejca.2013.11.039","volume":"50","author":"A Tolcher","year":"2014","unstructured":"Tolcher A, Goldman J, Patnaik A, Papadopoulos KP, Westwood P, Kelly CS et al (2014). A phase I trial of LY2584702 tosylate, a p70 S6 kinase inhibitor, in patients with advanced solid tumours. Eur J Cancer 50: 867\u2013875.","journal-title":"Eur J Cancer"},{"key":"BFnpp2015369_CR33","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1038\/nm.3353","volume":"19","author":"T Udagawa","year":"2013","unstructured":"Udagawa T, Farny NG, Jakovcevski M, Kaphzan H, Alarcon JM, Anilkumar S et al (2013). Genetic and acute CPEB1 depletion ameliorate fragile X pathophysiology. Nat Med 19: 1473\u20131477.","journal-title":"Nat Med"}],"container-title":["Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/npp2015369.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/npp2015369","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/npp2015369.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T23:53:55Z","timestamp":1684454035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/npp2015369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,28]]},"references-count":33,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["BFnpp2015369"],"URL":"https:\/\/doi.org\/10.1038\/npp.2015.369","relation":{},"ISSN":["0893-133X","1740-634X"],"issn-type":[{"value":"0893-133X","type":"print"},{"value":"1740-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,28]]},"assertion":[{"value":"12 October 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2015","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2015","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}