Lovastatin Corrects Excess Protein Synthesis and Prevents Epileptogenesis in a Mouse Model of Fragile X Syndrome
Many neuropsychiatric symptoms of fragile X syndrome (FXS) are believed to be a consequence of altered regulation of protein synthesis at synapses. We discovered that lovastatin, a drug that is widely prescribed for the treatment of high cholesterol, can correct excess hippocampal protein synthesis...
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| Veröffentlicht in: | Neuron (Cambridge, Mass.) Mass.), 2013-01, Vol.77 (2), p.243-250 |
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| container_title | Neuron (Cambridge, Mass.) |
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| creator | Osterweil, Emily K. Chuang, Shih-Chieh Chubykin, Alexander A. Sidorov, Michael Bianchi, Riccardo Wong, Robert K.S. Bear, Mark F. |
| description | Many neuropsychiatric symptoms of fragile X syndrome (FXS) are believed to be a consequence of altered regulation of protein synthesis at synapses. We discovered that lovastatin, a drug that is widely prescribed for the treatment of high cholesterol, can correct excess hippocampal protein synthesis in the mouse model of FXS and can prevent one of the robust functional consequences of increased protein synthesis in FXS, epileptogenesis. These data suggest that lovastatin is potentially disease modifying and could be a viable prophylactic treatment for epileptogenesis in FXS.
► Epilepsy is one consequence of excess protein synthesis in the Fmr1−/y mouse ► Lovastatin inhibits Ras-ERK1/2 and normalizes protein synthesis ► Lovastatin prevents epileptogenesis in the Fmr1−/y mouse ► Lovastatin, approved for human use, is potentially disease modifying in FXS
Osterweil et al. show that lovastatin, a widely prescribed HMG-CoA reductase inhibitor (statin), can correct multiple pathological changes in the mouse model of fragile X syndrome, including the induction of epilepsy (epileptogenesis). |
| doi_str_mv | 10.1016/j.neuron.2012.01.034 |
| format | Article |
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► Epilepsy is one consequence of excess protein synthesis in the Fmr1−/y mouse ► Lovastatin inhibits Ras-ERK1/2 and normalizes protein synthesis ► Lovastatin prevents epileptogenesis in the Fmr1−/y mouse ► Lovastatin, approved for human use, is potentially disease modifying in FXS
Osterweil et al. show that lovastatin, a widely prescribed HMG-CoA reductase inhibitor (statin), can correct multiple pathological changes in the mouse model of fragile X syndrome, including the induction of epilepsy (epileptogenesis).</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/j.neuron.2012.01.034</identifier><identifier>PMID: 23352161</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Autism ; Disease Models, Animal ; Epilepsy - genetics ; Epilepsy - metabolism ; Epilepsy - prevention & control ; Experiments ; Fragile X Syndrome - drug therapy ; Fragile X Syndrome - genetics ; Fragile X Syndrome - metabolism ; Genotype & phenotype ; Kinases ; Lovastatin - pharmacology ; Lovastatin - therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Protein Biosynthesis - drug effects ; Protein Biosynthesis - physiology ; Protein synthesis ; Proteins</subject><ispartof>Neuron (Cambridge, Mass.), 2013-01, Vol.77 (2), p.243-250</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Jan 23, 2013</rights><rights>2013 Elsevier Inc. All rights reserved. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c590t-3523e5a768d851ba7683d23eb4b9dafc45a36e7081f1d0f3c0ed2da15c06a6483</citedby><cites>FETCH-LOGICAL-c590t-3523e5a768d851ba7683d23eb4b9dafc45a36e7081f1d0f3c0ed2da15c06a6483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0896627313000408$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23352161$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Osterweil, Emily K.</creatorcontrib><creatorcontrib>Chuang, Shih-Chieh</creatorcontrib><creatorcontrib>Chubykin, Alexander A.</creatorcontrib><creatorcontrib>Sidorov, Michael</creatorcontrib><creatorcontrib>Bianchi, Riccardo</creatorcontrib><creatorcontrib>Wong, Robert K.S.</creatorcontrib><creatorcontrib>Bear, Mark F.</creatorcontrib><title>Lovastatin Corrects Excess Protein Synthesis and Prevents Epileptogenesis in a Mouse Model of Fragile X Syndrome</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>Many neuropsychiatric symptoms of fragile X syndrome (FXS) are believed to be a consequence of altered regulation of protein synthesis at synapses. We discovered that lovastatin, a drug that is widely prescribed for the treatment of high cholesterol, can correct excess hippocampal protein synthesis in the mouse model of FXS and can prevent one of the robust functional consequences of increased protein synthesis in FXS, epileptogenesis. These data suggest that lovastatin is potentially disease modifying and could be a viable prophylactic treatment for epileptogenesis in FXS.
► Epilepsy is one consequence of excess protein synthesis in the Fmr1−/y mouse ► Lovastatin inhibits Ras-ERK1/2 and normalizes protein synthesis ► Lovastatin prevents epileptogenesis in the Fmr1−/y mouse ► Lovastatin, approved for human use, is potentially disease modifying in FXS
Osterweil et al. show that lovastatin, a widely prescribed HMG-CoA reductase inhibitor (statin), can correct multiple pathological changes in the mouse model of fragile X syndrome, including the induction of epilepsy (epileptogenesis).</description><subject>Animals</subject><subject>Autism</subject><subject>Disease Models, Animal</subject><subject>Epilepsy - genetics</subject><subject>Epilepsy - metabolism</subject><subject>Epilepsy - prevention & control</subject><subject>Experiments</subject><subject>Fragile X Syndrome - drug therapy</subject><subject>Fragile X Syndrome - genetics</subject><subject>Fragile X Syndrome - metabolism</subject><subject>Genotype & phenotype</subject><subject>Kinases</subject><subject>Lovastatin - pharmacology</subject><subject>Lovastatin - therapeutic use</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Protein Biosynthesis - drug effects</subject><subject>Protein Biosynthesis - physiology</subject><subject>Protein synthesis</subject><subject>Proteins</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1v1DAQtRCIbgv_AKFIXLgkeBLbiS9IaNVSpEUgARI3y2tPtl5l7WAnK_rvcdhSPg5cbOvNmzfz_Ah5BrQCCuLVvvI4x-CrmkJdUahowx6QFVDZlgykfEhWtJOiFHXbnJHzlPaUAuMSHpOzuml4DQJWZNyEo06Tnpwv1iFGNFMqLr8bTKn4GMOEGf9066cbTC4V2tuM4hH9whrdgOMUduh_FjNTF-_DnDCfFoci9MVV1LvMKr4uIjaGAz4hj3o9JHx6d1-QL1eXn9fX5ebD23frN5vScEmnMu_XINet6GzHYbs8GpuhLdtKq3vDuG4EtrSDHiztG0PR1lYDN1Rowbrmgrw-6Y7z9oDW5JWjHtQY3UHHWxW0U39XvLtRu3BUDZctYywLvLwTiOHbjGlSB5cMDoP2mE0qEJwJCZ1cZr34h7oPc_TZXmYxnr0I4JnFTiwTQ0oR-_tlgKolUrVXp0jVEqmioHKkue35n0bum35l-Nsp5u88OowqGYfeoHVLnMoG9_8JPwBRALZE</recordid><startdate>20130123</startdate><enddate>20130123</enddate><creator>Osterweil, Emily K.</creator><creator>Chuang, Shih-Chieh</creator><creator>Chubykin, Alexander A.</creator><creator>Sidorov, Michael</creator><creator>Bianchi, Riccardo</creator><creator>Wong, Robert K.S.</creator><creator>Bear, Mark F.</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20130123</creationdate><title>Lovastatin Corrects Excess Protein Synthesis and Prevents Epileptogenesis in a Mouse Model of Fragile X Syndrome</title><author>Osterweil, Emily K. ; 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We discovered that lovastatin, a drug that is widely prescribed for the treatment of high cholesterol, can correct excess hippocampal protein synthesis in the mouse model of FXS and can prevent one of the robust functional consequences of increased protein synthesis in FXS, epileptogenesis. These data suggest that lovastatin is potentially disease modifying and could be a viable prophylactic treatment for epileptogenesis in FXS.
► Epilepsy is one consequence of excess protein synthesis in the Fmr1−/y mouse ► Lovastatin inhibits Ras-ERK1/2 and normalizes protein synthesis ► Lovastatin prevents epileptogenesis in the Fmr1−/y mouse ► Lovastatin, approved for human use, is potentially disease modifying in FXS
Osterweil et al. show that lovastatin, a widely prescribed HMG-CoA reductase inhibitor (statin), can correct multiple pathological changes in the mouse model of fragile X syndrome, including the induction of epilepsy (epileptogenesis).</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23352161</pmid><doi>10.1016/j.neuron.2012.01.034</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Autism Disease Models, Animal Epilepsy - genetics Epilepsy - metabolism Epilepsy - prevention & control Experiments Fragile X Syndrome - drug therapy Fragile X Syndrome - genetics Fragile X Syndrome - metabolism Genotype & phenotype Kinases Lovastatin - pharmacology Lovastatin - therapeutic use Male Mice Mice, Inbred C57BL Mice, Knockout Protein Biosynthesis - drug effects Protein Biosynthesis - physiology Protein synthesis Proteins |
| title | Lovastatin Corrects Excess Protein Synthesis and Prevents Epileptogenesis in a Mouse Model of Fragile X Syndrome |
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