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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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Posted ContentDOI

UBE3A–mediated p18/LAMTOR1 ubiquitination and degradation regulate mTORC1 activity and synaptic plasticity

TL;DR: Ube3a regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator, which is critical for typical synaptic plasticity and dendritic spine development.
Book ChapterDOI

Molecular mechanisms underlying cannabis-induced risk of psychosis

TL;DR: In this paper , the Akt/mTOR/S6 pathway was found to mediate the THC effects to turn the signaling of 5-HT2AR from the canonical non-hallucinogenic Gαq/11-proteins activation to the hallucinogenic gαi/o-protein-dependent response.
Posted ContentDOI

mTOR-RhoA signalling impairments in direct striatal projection neurons induce altered behaviours and striatal physiology in mice

TL;DR: Deep behavioural changes in absence of mTOR in dMSNs such as decreased spontaneous locomotion, impaired social interaction and repetitive behaviour are indicated, which identify mTOR RhoA signaling as an important regulator of striatal functions through an intricate mechanism involving RHoA and culminating in Kv1.1 overfunction, which could be targeted to treat striatal-related mTORopathies.
Journal ArticleDOI

Prenatal stress aggravates age-dependent cognitive decline, insulin signaling dysfunction, and the pro-inflammatory response in the APPNL-F/NL-F mouse model of Alzheimer's disease

TL;DR: In this article , an increase in the Aβ42/Aβ40 ratio and mouse ApoE levels in the hippocampus and frontal cortex preceded the onset of cognitive deficits in the KI mice.
Journal ArticleDOI

Embryonic mercury exposure in zebrafish: Alteration of metabolites and gene expression, related to visual and behavioral impairments.

TL;DR: In this paper , the authors showed that exposure of zebrafish larvae to 100 nM mercury chloride from gastrulation to hatching increased locomotor activity in the dark, reduced shoaling and exploratory behavior, and impaired color preference.
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.
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.
Journal ArticleDOI

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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