Journal ArticleDOI
mTOR complexes in neurodevelopmental and neuropsychiatric disorders
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TLDR
The most recent advances in studies of mTOR signaling in the brain and the possible mechanisms underlying the many different functions of the mTOR complexes in neurological diseases are described and the medical relevance is discussed.Abstract:
The mechanistic target of rapamycin (mTOR) acts as a highly conserved signaling "hub" that integrates neuronal activity and a variety of synaptic inputs. mTOR is found in two functionally distinct complexes, mTORC1 and mTORC2, that crucially control long-term synaptic efficacy and memory storage. Dysregulation of mTOR signaling is associated with neurodevelopmental and neuropsychiatric disorders. In this Review, we describe the most recent advances in studies of mTOR signaling in the brain and the possible mechanisms underlying the many different functions of the mTOR complexes in neurological diseases. In addition, we discuss the medical relevance of these findings.read more
Citations
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Translational Control in Synaptic Plasticity and Cognitive Dysfunction
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mTOR in Brain Physiology and Pathologies
Joël Bockaert,Philippe Marin +1 more
TL;DR: Preclinical and preliminary clinical studies indicate that inhibition of mTORC1 can be beneficial for some pathological conditions such as epilepsy, cognitive impairment, and brain tumors, whereas stimulation of m TORC1 (direct or indirect) can bebeneficial for other pathologies such as depression or axonal growth and regeneration.
References
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Journal ArticleDOI
NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses
Anita E. Autry,Megumi Adachi,Elena Nosyreva,Elisa S. Na,Maarten F. Los,Pengfei Cheng,Ege T. Kavalali,Lisa M. Monteggia +7 more
TL;DR: It is shown that ketamine and other NMDAR antagonists produce fast-acting behavioural antidepressant-like effects in mouse models, and that these effects depend on the rapid synthesis of brain-derived neurotrophic factor, suggesting the regulation of protein synthesis by spontaneous neurotransmission may serve as a viable therapeutic target for the development of fast- acting antidepressants.
Journal ArticleDOI
RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs.
TL;DR: It is proposed that RAFT1 is the direct target of FKBP12-rapamycin and a mammalian homolog of the TOR proteins, which were originally identified by mutations that confer rapamycin resistance in yeast.
Journal ArticleDOI
Chronic antidepressant administration increases the expression of camp response element binding protein (creb) in rat hippocampus
TL;DR: Findings indicate that upregulation of CREB is a common action of chronic antidepressant treatments that may lead to regulation of specific target genes, such as BDNF and trkB, and to the long-term effects of these treatments on brain function.
Journal ArticleDOI
A unifying model for mTORC1-mediated regulation of mRNA translation
Carson C. Thoreen,Lynne Chantranupong,Lynne Chantranupong,Heather R. Keys,Heather R. Keys,Timothy C. Wang,Nathanael S. Gray,David M. Sabatini,David M. Sabatini +8 more
TL;DR: mTORC1 as mentioned in this paper is shown to regulate a translational program that requires the rapamycin-resistant 4E-BP family of translational repressors and consists almost entirely of mRNAs containing 5′ terminal oligopyrimidine or related motifs.
Journal ArticleDOI
DEPTOR Is an mTOR Inhibitor Frequently Overexpressed in Multiple Myeloma Cells and Required for Their Survival
Timothy R. Peterson,Mathieu Laplante,Carson C. Thoreen,Yasemin Sancak,Seong A. Kang,W. Michael Kuehl,Nathanael S. Gray,David M. Sabatini +7 more
TL;DR: A novel mTOR-interacting protein whose deregulated overexpression in multiple myeloma cells represents a mechanism for activating PI3K/Akt signaling and promoting cell survival.
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