Journal ArticleDOI
mTOR complexes in neurodevelopmental and neuropsychiatric disorders
Reads0
Chats0
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
More filters
Journal ArticleDOI
Translational Control in the Brain in Health and Disease.
TL;DR: The general principles of neuronal translation are reviewed, focusing on the particular relevance of several key regulators of nervous system translation, including eukaryotic initiation factor 2α (eIF2α), the mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1), and the eUKaryotic elongation factor 2 (eEF2).
Journal ArticleDOI
Reduced protein synthesis in schizophrenia patient-derived olfactory cells
Jane A. English,Yongjun Fan,Melanie Föcking,Lorna M. Lopez,Magdalena Hryniewiecka,Kieran Wynne,Patrick Dicker,Nicholas Matigian,Gerard Cagney,Alan Mackay-Sim,David Cotter +10 more
TL;DR: Data from proteomic, transcriptomic, and functional assays from schizophrenia patient-derived ONS cells with genomics data are integrated to implicate dysregulated protein synthesis for the first time in schizophrenia.
Journal ArticleDOI
Mechanistically distinct cancer-associated mTOR activation clusters predict sensitivity to rapamycin
Jianing Xu,Can G. Pham,Steven K. Albanese,Yiyu Dong,Toshinao Oyama,Chung-Han Lee,Vanessa Rodrik-Outmezguine,Zhan Yao,Song Han,David J. Chen,Daniel L. Parton,John D. Chodera,Neal Rosen,Emily H. Cheng,James J. Hsieh +14 more
TL;DR: In this paper, the authors identified three distinct mechanisms of hyperactivation, including reduced binding to DEP domain-containing MTOR-interacting protein (DEPTOR), resistance to regulatory associated protein of mTOR-mediated (RAPTOR)-mediated) suppression, and altered kinase kinetics.
Journal ArticleDOI
mTOR-Dependent Cell Proliferation in the Brain
Larisa Ryskalin,Gloria Lazzeri,Marina Flaibani,Francesca Biagioni,Stefano Gambardella,Alessandro Frati,Francesco Fornai +6 more
TL;DR: Experimental and pathological findings suggest that mTOR upregulation plays a major role in determining an aggressive phenotype, thus determining relapse and chemoresistance in GBM malignancy.
Journal ArticleDOI
miR-199a Links MeCP2 with mTOR Signaling and Its Dysregulation Leads to Rett Syndrome Phenotypes.
Keita Tsujimura,Koichiro Irie,Hideyuki Nakashima,Yoshihiro Egashira,Yoichiro Fukao,Masayuki Fujiwara,Masayuki Itoh,Masahiro Uesaka,Takuya Imamura,Yasukazu Nakahata,Yui Yamashita,Takaya Abe,Shigeo Takamori,Kinichi Nakashima,Kinichi Nakashima +14 more
TL;DR: It is shown here that MeCP2 promotes the posttranscriptional processing of particular microRNAs (miRNAs) as a component of the microprocessor Drosha complex and establishes miR-199a as a critical downstream target of Me CP2 in RTT pathogenesis by linking MeCP1 with mTOR signaling.
References
More filters
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.
Related Papers (5)
mTOR signaling: at the crossroads of plasticity, memory and disease.
Charles A. Hoeffer,Eric Klann +1 more