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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Journal ArticleDOI
mTORC1 and mTORC2 have largely distinct functions in Purkinje cells
TL;DR: It is found that the two mouse models largely differ from each other by phenotype and cellular responses, which highlights a convergence between the phenotypes of Purkinje cells lacking mTORC1 activity and those expressing constitutively active m TORC1 due to TSC1 deficiency.
Journal ArticleDOI
UBE3A-mediated p18/LAMTOR1 ubiquitination and degradation regulate mTORC1 activity and synaptic plasticity.
Jiandong Sun,Yan Liu,Yousheng Jia,Xiaoning Hao,Wei ju Lin,Jennifer Tran,Gary Lynch,Michel Baudry,Xiaoning Bi +8 more
TL;DR: Results indicate that Ube3a-mediated regulation of p18 and subsequent mTORC1 signaling is critical for typical synaptic plasticity, dendritic spine development, and learning and memory.
Journal ArticleDOI
GABARAPs dysfunction by autophagy deficiency in adolescent brain impairs GABAA receptor trafficking and social behavior
Kelvin Hui,Noriko Takashima,Akiko Watanabe,Thomas E. Chater,Hiroshi Matsukawa,Yoko Nekooki-Machida,Per Nilsson,Ryo Endo,Yukiko Goda,Takaomi C. Saido,Takeo Yoshikawa,Motomasa Tanaka +11 more
TL;DR: This work demonstrates a novel physiological role for autophagy in regulating GABA signaling beyond postnatal neurodevelopment, providing a potential mechanism for the reduced inhibitory inputs observed in neurodevelopmental and neuropsychiatric disorders with mTOR hyperactivation.
Journal ArticleDOI
Epilepsy and Neurodevelopmental Comorbidities in Tuberous Sclerosis Complex: A Natural History Study.
Ajay Gupta,Gwendolyn de Bruyn,Simon Tousseyn,Simon Tousseyn,Balu Krishnan,Lieven Lagae,Nitin Agarwal,Michael Frost,Steven Sparagana,Josiane LaJoie,James J. Riviello,Orrin Devinsky,Elizabeth A. Thiele,William McClintock,Michael Kohrman,Candida Brown,Rachel Kuperman,Joyce Y. Wu,Hope Northrup,E. Martina Bebin,Bruce R. Korf,Paul Levisohn,Susan Koh,Ian Miller,Michael Duchowny,Stephen Ashwal,Anna Jansen,Peter B. Crino,John D. Pollard,Katherine L. Nathanson,Mustafa Sahin,Darcy A. Krueger,Michael Wong,Anna Jeong +33 more
TL;DR: Epilepsy is associated with intellectual disability, and when epilepsy begins before age two years the frequency and severity of intellectual disability is much higher.
Journal ArticleDOI
Collybistin binds and inhibits mTORC1 signaling: a potential novel mechanism contributing to intellectual disability and autism
Camila Oliveira Freitas Machado,Karina Griesi-Oliveira,Carla Rosenberg,Fernando Kok,Stephanie Martins,Maria Rita Passos-Bueno,Andréa L. Sertié +6 more
TL;DR: Induced pluripotent stem cell-derived neural progenitor cells from a male patient with a deletion of entire CB gene and from control individuals, as well as a heterologous expression system, are described that CB physically interacts with mTOR and inhibits mTORC1 signaling pathway and protein synthesis.
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.
Dos D. Sarbassov,Siraj M. Ali,Siraj M. Ali,Shomit Sengupta,Shomit Sengupta,Joon Ho Sheen,Joon Ho Sheen,Peggy P. Hsu,Peggy P. Hsu,Alex F. Bagley,Alex F. Bagley,Andrew L. Markhard,Andrew L. Markhard,David M. Sabatini,David M. Sabatini +14 more
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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