| Deregulated mTOR-mediated translation in intellectual disability. | |
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MedLine Citation:
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PMID: 22285767 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Local translation of dendritic mRNAs is a key aspect of dendrite and spine morphogenesis and synaptic plasticity, two phenomena generally compromised in intellectual disability disorders. Mammalian target of rapamycin (mTOR) is a protein kinase involved in a plethora of functions including dendritogenesis, plasticity and the regulation of local translation. Hence, this kinase may well be implicated in intellectual disability. Hyperactivation of mTOR has been recently reported in mouse models of Fragile X and tuberous sclerosis, two important causes of intellectual disability. Moreover, local dendritic translation seems to be increased in Fragile X syndrome. Recent findings show that the mTOR pathway is also deregulated in murine models of Rett's syndrome and Down's syndrome. As in Fragile X, local dendritic translation seems to be abnormally active in Down's syndrome mice, while rapamycin, a Food and Drug Administration-approved mTOR inhibitor, restores normal rates of translation. Rapamycin administration in tuberous sclerosis mice rescues deficits in behavior and synaptic plasticity. Indeed, mTOR-dependent deregulation of local translation may be a common trait in different intellectual deficiencies, suggesting that mTOR inhibitors may have significant therapeutic potential for the treatment of diverse forms of cognitive impairment. |
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Authors:
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José Antonio Troca-Marín; Alexandra Alves-Sampaio; María Luz Montesinos |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-25 |
Journal Detail:
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Title: Progress in neurobiology Volume: - ISSN: 1873-5118 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370121 Medline TA: Prog Neurobiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier Ltd. |
Affiliation:
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Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Av. Sánchez-Pizjuán 4, E-41009 Sevilla, Spain. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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