PMID- 22285767
OWN - NLM
STAT- MEDLINE
DCOM- 20120605
LR  - 20220330
IS  - 1873-5118 (Electronic)
IS  - 0301-0082 (Linking)
VI  - 96
IP  - 2
DP  - 2012 Feb
TI  - Deregulated mTOR-mediated translation in intellectual disability.
PG  - 268-82
LID - 10.1016/j.pneurobio.2012.01.005 [doi]
AB  - 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.
CI  - Copyright A(c) 2012 Elsevier Ltd. All rights reserved.
FAU - Troca-Marin, Jose Antonio
AU  - Troca-Marin JA
AD  - Departamento de Fisiologia Medica y Biofisica, Universidad de Sevilla, Av. 
      Sanchez-Pizjuan 4, E-41009 Sevilla, Spain.
FAU - Alves-Sampaio, Alexandra
AU  - Alves-Sampaio A
FAU - Montesinos, Maria Luz
AU  - Montesinos ML
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120125
PL  - England
TA  - Prog Neurobiol
JT  - Progress in neurobiology
JID - 0370121
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Dendrites/metabolism/ultrastructure
MH  - Down Syndrome/physiopathology
MH  - Fragile X Syndrome/physiopathology
MH  - Intellectual Disability/drug therapy/*genetics/*physiopathology
MH  - Neuronal Plasticity/physiology
MH  - Protein Biosynthesis/*physiology
MH  - RNA, Messenger/metabolism
MH  - Rett Syndrome/physiopathology
MH  - Sirolimus/therapeutic use
MH  - Synapses/physiology/ultrastructure
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/genetics/*metabolism
MH  - Tuberous Sclerosis/physiopathology
EDAT- 2012/01/31 06:00
MHDA- 2012/06/06 06:00
CRDT- 2012/01/31 06:00
PHST- 2011/10/09 00:00 [received]
PHST- 2012/01/02 00:00 [revised]
PHST- 2012/01/12 00:00 [accepted]
PHST- 2012/01/31 06:00 [entrez]
PHST- 2012/01/31 06:00 [pubmed]
PHST- 2012/06/06 06:00 [medline]
AID - S0301-0082(12)00006-8 [pii]
AID - 10.1016/j.pneurobio.2012.01.005 [doi]
PST - ppublish
SO  - Prog Neurobiol. 2012 Feb;96(2):268-82. doi: 10.1016/j.pneurobio.2012.01.005. Epub 
      2012 Jan 25.