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Journal ArticleDOI

mTOR complexes in neurodevelopmental and neuropsychiatric disorders

Mauro Costa-Mattioli, +1 more
- 01 Nov 2013 - 
- Vol. 16, Iss: 11, pp 1537-1543
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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.

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Citations
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Protein Phosphorylation Signaling Cascades in Autism: The Role of mTOR Pathway.

TL;DR: In this article, the authors analyzed the studies on the molecular abnormalities of the mTOR-associated signaling cascades in autism spectrum disorders (ASDs) and outlined the prospects for the pathogenicity-targeting pharmacotherapeutic approaches to ASDs, in particular syndromic ASDs.
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Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse model.

TL;DR: In this paper, the authors characterized the proteome of hippocampal synaptoneurosomes from these mice, and found a predicted alteration of synaptic plasticity pathways, including long-term depression (LTD).
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Effects of intrathecal injection of rapamycin on pain threshold and spinal cord glial activation in rats with neuropathic pain.

TL;DR: Intrathecal injection of rapamycin may attenuate CCI-induced hyperalgesia and inhibit the activation of astrocyte.
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Palladin Is a Neuron-Specific Translational Target of mTOR Signaling That Regulates Axon Morphogenesis.

TL;DR: This study identifies a novel mechanism of neuronal morphogenesis regulated by mTOR signaling through control of translation of the key protein palladin, which is localized within the cell body and axons in hippocampal neurons.
References
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mTOR Signaling in Growth Control and Disease

TL;DR: The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis as mentioned in this paper, and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration.
Journal ArticleDOI

mTOR signaling in growth control and disease.

TL;DR: Recent advances in understanding of the mTOR pathway are reviewed and pharmacological approaches to treat human pathologies linked to mTOR deregulation are discussed.
Journal ArticleDOI

The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses

TL;DR: This book aims to investigate elementary forms of learning and memory at a cellular molecular level—as specific molecular activities within identified nerve cells withinidentified nerve cells.
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Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets

TL;DR: Recent advances in understanding of the molecular structures and biochemical functions of the translation initiation machinery are described and key strategies that mediate general or gene-specific translational control are summarized, particularly in mammalian systems.
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Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB.

TL;DR: It is shown that rapamycin inhibits the assembly of mTORC2 and that, in many cell types, prolongedRapamycin treatment reduces the levels of m TORC2 below those needed to maintain Akt/PKB signaling.
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