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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Neurobiology of addiction: A neurocircuitry analysis.
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TL;DR: Molecular genetic studies have identified transduction and transcription factors that act in neurocircuitry associated with the development and maintenance of addiction that might mediate initial vulnerability, maintenance, and relapse associated with addiction.
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Immune mediators in the brain and peripheral tissues in autism spectrum disorder
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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
Activation of mammalian target of rapamycin in cytomegalic neurons of human cortical dysplasia.
M. Cecilia Ljungberg,Meenakshi B. Bhattacharjee,Yaojuan Lu,Dawna L. Armstrong,Daniel Yoshor,John W. Swann,Michael Sheldon,Gabriella D'Arcangelo,Gabriella D'Arcangelo +8 more
TL;DR: This study sought to identify molecular markers of cytomegalic neurons in focal or hemispheric cortical dysplasia and to determine whether the activity of the mammalian target of rapamycin (mTOR) kinase is abnormally high in these cells.
Journal ArticleDOI
Removal of S6K1 and S6K2 Leads to Divergent Alterations in Learning, Memory, and Synaptic Plasticity.
Marcia D. Antion,Maayan Merhav,Charles A. Hoeffer,Charles A. Hoeffer,Gerald Reis,Sara C. Kozma,George Thomas,Erin M. Schuman,Kobi Rosenblum,Eric Klann +9 more
TL;DR: The findings demonstrate that removal of S6K1 leads to a distinct array of behavioral and synaptic plasticity phenotypes that are not mirrored by the removal ofS6K2, and suggest that neither gene by itself is required for L-LTP but instead may be required for other types of synaptic Plasticity required for cognitive processing.
Journal ArticleDOI
Neocortical hyperexcitability in a human case of tuberous sclerosis complex and mice lacking neuronal expression of TSC1
Yanling Wang,Joel S. F. Greenwood,Maria Elisa Calcagnotto,Heidi E. Kirsch,Nicholas M. Barbaro,Scott C. Baraban +5 more
TL;DR: Examining excitatory and inhibitory synaptic currents in human tissue samples obtained from a TSC patient with no discernible cortical tubers and acute neocortical brain slices from a mouse featuring synapsin‐driven conditional deletion of a T SC1 gene was designed to assess whether TSC gene inactivation alters excitability.
Journal ArticleDOI
Phase I and pharmacokinetic study of CCI-779, a novel cytostatic cell-cycle inhibitor, in combination with 5-fluorouracil and leucovorin in patients with advanced solid tumors
TL;DR: The safety profiles of CCI-779 and 5-FU/LV suggest an overlap of drug-related toxicities, and the administration of these drugs at these doses and schedule resulted in unacceptable toxicity and therefore cannot be recommended.
Journal ArticleDOI
Role for mTOR Signaling and Neuronal Activity in Morphine-Induced Adaptations in Ventral Tegmental Area Dopamine Neurons
Michelle S. Mazei-Robison,Ja Wook Koo,Allyson K. Friedman,Carien S. Lansink,Alfred J. Robison,Monika Vinish,Vaishnav Krishnan,Seyun Kim,Michael A. Siuta,Aurelio Galli,Kevin D. Niswender,Raghu Appasani,Monika Cs. Horvath,Rachael L. Neve,Paul F. Worley,Solomon H. Snyder,Yasmin L. Hurd,Joseph F. Cheer,Ming-Hu Han,Scott J. Russo,Eric J. Nestler +20 more
TL;DR: Local knockout of Rictor in VTA decreases DA soma size and reduces rewarding responses to morphine, consistent with the hypothesis that these adaptations represent a mechanism of reward tolerance, and demonstrate a novel role for AKT-mTORC2 signaling in mediating neuroadaptations to opiate drugs of abuse.
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