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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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UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling.

TL;DR: UBTOR depletion activates mTOR signaling and promotes cell growth, whilst UBTOR overexpression suppresses colony formation in cancer cell lines and promotes tumor growth and m TOR signaling in a xenograft mouse model.
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The genetics and neurobiology of ESSENCE: The third Birgit Olsson lecture.

TL;DR: Five main pathways are associated with ASD and ID: chromatin remodelling, cytoskeleton dynamics, mRNA translation, metabolism and synapse formation/function, and three propositions coming from institutions, researchers and/or communities of patients and families to foster research are detailed.
Journal ArticleDOI

mTOR kinase activity disrupts a phosphorylation signaling network in schizophrenia brain.

TL;DR: In this paper, the authors investigated the role of mTOR kinase activity by inhibiting it with rapamycin in postmortem tissue and compared the impact of the mTOR inhibition in SZ and comparison subjects using kinome arrays.
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Ribosomal Protein S6 Hypofunction in Postmortem Human Brain Links mTORC1-Dependent Signaling and Schizophrenia.

TL;DR: Findings provide further evidence for the involvement of the mTOR-dependent signaling pathway in schizophrenia and suggest that a hypofunctional S6 may have a role in the etiopathogenesis of this disorder.
Journal ArticleDOI

Posttranscriptional Gene Regulation of the GABA Receptor to Control Neuronal Inhibition.

TL;DR: It is proposed that local (co)-translational control mechanism might control transmission of inhibitory synapses through known aspects of posttranscriptional regulation and protein dynamics of the GABA receptor (GABAR).
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.
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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.
Journal ArticleDOI

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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