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
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References
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Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome
Fabian Fernandez,Wade Morishita,Elizabeth Zuniga,James Nguyen,Martina Blank,Robert C. Malenka,Craig C. Garner +6 more
TL;DR: It is shown that chronic systemic treatment of Ts65Dn mice with GABAA antagonists at non-epileptic doses causes a persistent post-drug recovery of cognition and long-term potentiation, suggesting that over-inhibition contributes to intellectual disabilities associated with Down syndrome.
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Activation of the Phosphoinositide 3-Kinase-Akt-Mammalian Target of Rapamycin Signaling Pathway Is Required for Metabotropic Glutamate Receptor-Dependent Long-Term Depression
Lingfei Hou,Eric Klann +1 more
TL;DR: The findings indicate that activation of the PI3K-Akt-mTOR signaling cascade is required for mGluR-LTD and suggest that this pathway may couple group I mGLURs to translation initiation in hippocampal area CA1.
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mTOR complex 2 signaling and functions
Won Jun Oh,Estela Jacinto +1 more
TL;DR: This review focuses on recent developments on mammalian mTORC2 signaling mechanisms and its cellular and tissue-specific functions and examines the contribution of this less-studied mTOR complex in cancer, metabolic disorders and aging.
Journal ArticleDOI
Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis
Journal ArticleDOI
Response of a Neuronal Model of Tuberous Sclerosis to Mammalian Target of Rapamycin (mTOR) Inhibitors: Effects on mTORC1 and Akt Signaling Lead to Improved Survival and Function
Lynsey Meikle,Kristen Pollizzi,Anna Egnor,Ioannis Kramvis,Heidi Lane,Mustafa Sahin,David J. Kwiatkowski +6 more
TL;DR: Rapamycin/RAD001 are highly effective therapies for this neuronal model of TSC, with benefit apparently attributable to effects on mTORC1 and Akt signaling and, consequently, cell size and myelination.
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