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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Rapamycin protects against Aβ-induced synaptotoxicity by increasing presynaptic activity in hippocampal neurons.
TL;DR: Under these conditions, rapamycin-treated hippocampal neurons are resistant to the synaptotoxic effect induced by Aβ oligomers, suggesting that enhancers of presynaptic activity can be therapeutic agents for Alzheimer's disease.
Journal ArticleDOI
Role of mTOR-Regulated Autophagy in Synaptic Plasticity Related Proteins Downregulation and the Reference Memory Deficits Induced by Anesthesia/Surgery in Aged Mice
Sunan Gao,Siyu Zhang,Hongmei Zhou,Tao Xiaoyan,Yunjian Ni,Daqing Pei,Shuai Kang,Weiwei Yan,Jian Lu +8 more
TL;DR: In this article, the authors explored whether rapamycin can ameliorate anesthesia/surgery-induced cognitive deficits by inhibiting mTOR, activating autophagy and rising synaptic plasticity-related proteins in the hippocampus.
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Translational control in brain pathologies: biological significance and therapeutic opportunities
TL;DR: This review provides a brief overview of the basic principles of mRNA translation, and discusses alterations of this process relevant to CNS disease conditions, with a focus on brain tumors and chronic neurological conditions.
Journal ArticleDOI
RAB39B Deficiency Impairs Learning and Memory Partially Through Compromising Autophagy.
Mengxi Niu,Naizhen Zheng,Zijie Wang,Yue Gao,Xianghua Luo,Zhicai Chen,Xing Fu,Yanyan Wang,Ting Wang,Manqing Liu,Tingting Yao,Peijie Yao,Jian Meng,Yunqiang Zhou,Yunlong Ge,Zhanxiang Wang,Qilin Ma,Huaxi Xu,Yun-wu Zhang +18 more
TL;DR: Treatment with rapamycin partially rescued impaired memory and synaptic plasticity in Rab39b KO mice and suggested that targeting autophagy may have potential for treating XLID caused by RAB39B loss-of-function mutations.
Journal ArticleDOI
Role of mTOR‐regulated autophagy in spine pruning defects and memory impairments induced by binge‐like ethanol treatment in adolescent mice
María Pascual,Rosa Lopez-Hidalgo,Sandra Montagud-Romero,Juan R. Ureña-Peralta,Marta Rodríguez-Arias,Consuelo Guerri +5 more
TL;DR: Results support the critical role of mTOR/autophagy dysfunctions in the dendritic spines alterations and cognitive alterations induced by binge alcohol in adolescence as well as Rapamycin administration prior to ethanol administration restores ethanol‐induced changes in both plasticity and behavior Dysfunctions.
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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