Thwarting dyskinesia by targeting mTORC1.

Abstract:

:In a mouse model of Parkinson's disease, new evidence shows that l-DOPA, which is used to treat the symptoms of the disease but also causes dyskinesia, results in a persistent activation of the protein kinase mTOR (mammalian target of rapamycin) in a subset of striatal medium spiny neurons. Moreover, blockade of a specific type of mTOR signaling (mTORC1) prevents the development of dyskinesia, but not the antiakinetic benefits produced by l-DOPA. Thus, mTORC1 may be a viable therapeutic target for dyskinesia caused by l-DOPA treatment in patients with Parkinson's disease.

journal_name

Sci Signal

journal_title

Science signaling

authors

Klann E

doi

10.1126/scisignal.280pe42

subject

Has Abstract

pub_date

2009-07-21 00:00:00

pages

pe42

issue

80

eissn

1945-0877

issn

1937-9145

pii

2/80/pe42

journal_volume

2

pub_type

杂志文章,评审
  • Transglutaminase-catalyzed protein-protein cross-linking suppresses the activity of the NF-κB-like transcription factor relish.

    abstract::Cross-linking of proteins by mammalian transglutaminases (TGs) plays important roles in physiological phenomena such as blood coagulation and skin formation. We show that Drosophila TG suppressed innate immune signaling in the gut. RNA interference (RNAi) directed against TG reduced the life span of flies reared under...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2003970

    authors: Shibata T,Sekihara S,Fujikawa T,Miyaji R,Maki K,Ishihara T,Koshiba T,Kawabata S

    更新日期:2013-07-23 00:00:00

  • The adaptor protein insulin receptor substrate 2 inhibits alternative macrophage activation and allergic lung inflammation.

    abstract::Insulin receptor substrate 2 (IRS2) is an adaptor protein that becomes tyrosine-phosphorylated in response to the cytokines interleukin-4 (IL-4) and IL-13, which results in activation of the phosphoinositide 3-kinase (PI3K)-Akt pathway. IL-4 and IL-13 contribute to allergic lung inflammation. To examine the role of IR...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aad6724

    authors: Dasgupta P,Dorsey NJ,Li J,Qi X,Smith EP,Yamaji-Kegan K,Keegan AD

    更新日期:2016-06-21 00:00:00

  • Rab13 acts downstream of the kinase Mst1 to deliver the integrin LFA-1 to the cell surface for lymphocyte trafficking.

    abstract::In lymphocytes, the kinase Mst1 is required for the proper organization of integrins in the plasma membrane at the leading edge of migrating cells, which is critical for lymphocyte trafficking. We found a functional link between the small G protein Rab13 and Mst1 in lymphocyte adhesion and migration. In response to st...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2005199

    authors: Nishikimi A,Ishihara S,Ozawa M,Etoh K,Fukuda M,Kinashi T,Katagiri K

    更新日期:2014-07-29 00:00:00

  • How Ca2+-permeable AMPA receptors, the kinase PKA, and the phosphatase PP2B are intertwined in synaptic LTP and LTD.

    abstract::Both synaptic long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical for memory formation. Dell'Acqua and co-workers now demonstrate that transient postsynaptic incorporation of Ca(2+)-permeable (CP) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is required for...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.aaf7067

    authors: Hell JW

    更新日期:2016-04-26 00:00:00

  • Visualizing immune system complexity.

    abstract::The European Molecular Biology Organization (EMBO) meeting Visualizing Immune System Complexity, held in January 2009, covered multiple scales, from imaging single molecules to imaging whole animals. In addition to experimental details, there was an emphasis on modeling both for data analysis and as a predictive tool ...

    journal_title:Science signaling

    pub_type:

    doi:10.1126/scisignal.266mr4

    authors: Dustin ML

    更新日期:2009-04-14 00:00:00

  • Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis.

    abstract::Deoxyhypusine synthase (DHPS) uses the polyamine spermidine to catalyze the hypusine modification of the mRNA translation factor eIF5A and promotes oncogenesis through poorly defined mechanisms. Because germline deletion of Dhps is embryonically lethal, its role in normal postnatal cellular function in vivo remains un...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aax0715

    authors: Levasseur EM,Yamada K,Piñeros AR,Wu W,Syed F,Orr KS,Anderson-Baucum E,Mastracci TL,Maier B,Mosley AL,Liu Y,Bernal-Mizrachi E,Alonso LC,Scott D,Garcia-Ocaña A,Tersey SA,Mirmira RG

    更新日期:2019-12-03 00:00:00

  • Drosophila toll pathway: the new model.

    abstract::In Drosophila, recognition of microbe-specific molecules (such as bacterial peptidoglycans) activates serine protease cascades that converge to activate the Toll pathway. Recent data show that the serine protease Grass, which is activated downstream of pattern recognition receptors and was initially thought to be a co...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.252jc1

    authors: Ashok Y

    更新日期:2009-01-06 00:00:00

  • mGluR5 antagonism increases autophagy and prevents disease progression in the zQ175 mouse model of Huntington's disease.

    abstract::Huntington's disease (HD) is a neurodegenerative disease caused by an expansion in the huntingtin protein (also called Htt) that induces neuronal cell death with age. We found that the treatment of 12-month-old symptomatic heterozygous and homozygous zQ175 huntingtin knockin mice for 12 weeks with CTEP, a negative all...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aan6387

    authors: Abd-Elrahman KS,Hamilton A,Hutchinson SR,Liu F,Russell RC,Ferguson SSG

    更新日期:2017-12-19 00:00:00

  • A phosphorylated pseudokinase complex controls cell wall synthesis in mycobacteria.

    abstract::Prokaryotic cell wall biosynthesis is coordinated with cell growth and division, but the mechanisms regulating this dynamic process remain obscure. Here, we describe a phosphorylation-dependent regulatory complex that controls peptidoglycan (PG) biosynthesis in Mycobacterium tuberculosis. We found that PknB, a PG-resp...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002525

    authors: Gee CL,Papavinasasundaram KG,Blair SR,Baer CE,Falick AM,King DS,Griffin JE,Venghatakrishnan H,Zukauskas A,Wei JR,Dhiman RK,Crick DC,Rubin EJ,Sassetti CM,Alber T

    更新日期:2012-01-24 00:00:00

  • Wingless promotes proliferative growth in a gradient-independent manner.

    abstract::Morphogens form concentration gradients that organize patterns of cells and control growth. It has been suggested that, rather than the intensity of morphogen signaling, it is its gradation that is the relevant modulator of cell proliferation. According to this view, the ability of morphogens to regulate growth during...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2000360

    authors: Baena-Lopez LA,Franch-Marro X,Vincent JP

    更新日期:2009-10-06 00:00:00

  • Discovering relationships between nuclear receptor signaling pathways, genes, and tissues in Transcriptomine.

    abstract::We previously developed a web tool, Transcriptomine, to explore expression profiling data sets involving small-molecule or genetic manipulations of nuclear receptor signaling pathways. We describe advances in biocuration, query interface design, and data visualization that enhance the discovery of uncharacterized biol...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aah6275

    authors: Becnel LB,Ochsner SA,Darlington YF,McOwiti A,Kankanamge WH,Dehart M,Naumov A,McKenna NJ

    更新日期:2017-04-25 00:00:00

  • Induction of metabolic quiescence defines the transitional to follicular B cell switch.

    abstract::Transitional B cells must actively undergo selection for self-tolerance before maturing into their resting follicular B cell successors. We found that metabolic quiescence was acquired at the follicular B cell stage in both humans and mice. In follicular B cells, the expression of genes involved in ribosome biogenesis...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaw5573

    authors: Farmer JR,Allard-Chamard H,Sun N,Ahmad M,Bertocchi A,Mahajan VS,Aicher T,Arnold J,Benson MD,Morningstar J,Barmettler S,Yuen G,Murphy SJH,Walter JE,Ghebremichael M,Shalek AK,Batista F,Gerszten R,Pillai S

    更新日期:2019-10-22 00:00:00

  • A large bioactive BMP ligand with distinct signaling properties is produced by alternative proconvertase processing.

    abstract::Dimers of conventional transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) ligands are composed of two 100- to 140-amino acid peptides that are produced through the proteolytic processing of a proprotein precursor by proconvertases, such as furin. We report the identification of an evolutionarily...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002549

    authors: Akiyama T,Marqués G,Wharton KA

    更新日期:2012-04-03 00:00:00

  • Tyrosine phosphorylation of the Gα-interacting protein GIV promotes activation of phosphoinositide 3-kinase during cell migration.

    abstract::GIV (Gα-interacting vesicle-associated protein; also known as Girdin) enhances Akt activation downstream of multiple growth factor- and G protein (heterotrimeric guanosine 5'-triphosphate-binding protein)-coupled receptors to trigger cell migration and cancer invasion. We demonstrate that GIV is a tyrosine phosphoprot...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002049

    authors: Lin C,Ear J,Pavlova Y,Mittal Y,Kufareva I,Ghassemian M,Abagyan R,Garcia-Marcos M,Ghosh P

    更新日期:2011-09-27 00:00:00

  • The chemokine CXCL12 generates costimulatory signals in T cells to enhance phosphorylation and clustering of the adaptor protein SLP-76.

    abstract::The CXC chemokine CXCL12 mediates the chemoattraction of T cells and enhances the stimulation of T cells through the T cell receptor (TCR). The adaptor SLP-76 [Src homology 2 (SH2) domain-containing leukocyte protein of 76 kD] has two key tyrosine residues, Tyr(113) and Tyr(128), that mediate signaling downstream of t...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2004018

    authors: Smith X,Schneider H,Köhler K,Liu H,Lu Y,Rudd CE

    更新日期:2013-07-30 00:00:00

  • RAS signaling promotes resistance to JAK inhibitors by suppressing BAD-mediated apoptosis.

    abstract::Myeloproliferative neoplasms (MPNs) frequently have an activating mutation in the gene encoding Janus kinase 2 (JAK2). Thus, targeting the pathway mediated by JAK and its downstream substrate, signal transducer and activator of transcription (STAT), may yield clinical benefit for patients with MPNs containing the JAK2...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2005301

    authors: Winter PS,Sarosiek KA,Lin KH,Meggendorfer M,Schnittger S,Letai A,Wood KC

    更新日期:2014-12-23 00:00:00

  • An introduction to MATLAB.

    abstract::This two-part lecture introduces students to the scientific computing language MATLAB. Prior computer programming experience is not required. The lectures present basic concepts of computer programming logic that tend to cause difficulties for beginners in addition to concepts that relate specifically to the MATLAB la...

    journal_title:Science signaling

    pub_type:

    doi:10.1126/scisignal.2001984

    authors: Sobie EA

    更新日期:2011-09-13 00:00:00

  • Mechanobiology of the skeleton.

    abstract::Mechanical loading of the skeleton is essential for the development, growth, and maintenance of strong, weight-bearing bones. Bone strength is plastic and can be modulated in adults, as illustrated by the increased bone mass in the playing arms of athletes as compared with their nonplaying arms. Our studies have shown...

    journal_title:Science signaling

    pub_type:

    doi:10.1126/scisignal.268pt3

    authors: Turner CH,Warden SJ,Bellido T,Plotkin LI,Kumar N,Jasiuk I,Danzig J,Robling AG

    更新日期:2009-04-28 00:00:00

  • Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

    abstract::The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteo...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2004088

    authors: Gao J,Aksoy BA,Dogrusoz U,Dresdner G,Gross B,Sumer SO,Sun Y,Jacobsen A,Sinha R,Larsson E,Cerami E,Sander C,Schultz N

    更新日期:2013-04-02 00:00:00

  • The GAS6-AXL signaling network is a mesenchymal (Mes) molecular subtype-specific therapeutic target for ovarian cancer.

    abstract::Ovarian cancer is a complex disease with heterogeneity among the gene expression molecular subtypes (GEMS) between patients. Patients with tumors of a mesenchymal ("Mes") subtype have a poorer prognosis than patients with tumors of an epithelial ("Epi") subtype. We evaluated GEMS of ovarian cancer patients for molecul...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf8175

    authors: Antony J,Tan TZ,Kelly Z,Low J,Choolani M,Recchi C,Gabra H,Thiery JP,Huang RY

    更新日期:2016-10-04 00:00:00

  • Long-term potentiation modulates synaptic phosphorylation networks and reshapes the structure of the postsynaptic interactome.

    abstract::The postsynaptic site of neurons is composed of more than 1500 proteins arranged in protein-protein interaction complexes, the composition of which is modulated by protein phosphorylation through the actions of complex signaling networks. Components of these networks function as key regulators of synaptic plasticity, ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf6716

    authors: Li J,Wilkinson B,Clementel VA,Hou J,O'Dell TJ,Coba MP

    更新日期:2016-08-09 00:00:00

  • CCR5 adopts three homodimeric conformations that control cell surface delivery.

    abstract::Biophysical methods and x-ray crystallography have revealed that class A G protein-coupled receptors (GPCRs) can form homodimers. We combined computational approaches with receptor cross-linking, energy transfer, and a newly developed functional export assay to characterize the residues involved in the dimerization in...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aal2869

    authors: Jin J,Momboisse F,Boncompain G,Koensgen F,Zhou Z,Cordeiro N,Arenzana-Seisdedos F,Perez F,Lagane B,Kellenberger E,Brelot A

    更新日期:2018-05-08 00:00:00

  • Tumor suppression by LKB1: SIK-ness prevents metastasis.

    abstract::The LKB1 serine-threonine kinase is a tumor suppressor that is inactivated in a large number of sporadic human lung non-small cell carcinomas (NSCLCs) and cervical cancers. Genetic deletion of LKB1 in various mouse tissues results in tumorigenesis, and loss of LKB1 increases metastasis in a mouse model of NSCLC. LKB1 ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.286pe55

    authors: Shaw RJ

    更新日期:2009-09-01 00:00:00

  • VGF, a new player in antidepressant action?

    abstract::Recent studies have identified adaptations of intracellular signaling pathways and target genes that could contribute or modulate the action of antidepressant drugs, as well as exercise-mediated antidepressant responses. Understanding these adaptations, particularly those changes that are common to diverse antidepress...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/stke.118pe19

    authors: Malberg JE,Monteggia LM

    更新日期:2008-05-06 00:00:00

  • Loss of MCU prevents mitochondrial fusion in G1-S phase and blocks cell cycle progression and proliferation.

    abstract::The role of the mitochondrial Ca2+ uniporter (MCU) in physiologic cell proliferation remains to be defined. Here, we demonstrated that the MCU was required to match mitochondrial function to metabolic demands during the cell cycle. During the G1-S transition (the cycle phase with the highest mitochondrial ATP output),...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aav1439

    authors: Koval OM,Nguyen EK,Santhana V,Fidler TP,Sebag SC,Rasmussen TP,Mittauer DJ,Strack S,Goswami PC,Abel ED,Grumbach IM

    更新日期:2019-04-30 00:00:00

  • FZD5 is a Gαq-coupled receptor that exhibits the functional hallmarks of prototypical GPCRs.

    abstract::Frizzleds (FZDs) are a group of seven transmembrane-spanning (7TM) receptors that belong to class F of the G protein-coupled receptor (GPCR) superfamily. FZDs bind WNT proteins to stimulate diverse signaling cascades involved in embryonic development, stem cell regulation, and adult tissue homeostasis. Frizzled 5 (FZD...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aar5536

    authors: Wright SC,Cañizal MCA,Benkel T,Simon K,Le Gouill C,Matricon P,Namkung Y,Lukasheva V,König GM,Laporte SA,Carlsson J,Kostenis E,Bouvier M,Schulte G,Hoffmann C

    更新日期:2018-12-04 00:00:00

  • Grooming and growing with microglia.

    abstract::Microglia mediate neuroprotection and neuropathogenesis but have not been directly associated with behavior. As gatekeepers of the brain's immune system, microglia protect the brain from pathogens but also contribute to inflammation, which may negatively affect neurons. A recent study demonstrates a role for Hoxb8-exp...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.3147jc8

    authors: Antony JM

    更新日期:2010-11-09 00:00:00

  • Focus issue: uncovering the mechanisms of neurological disease.

    abstract::This week, Science Signaling highlights research that uses computational and cell biology approaches to uncover the molecular mechanisms underlying diseases of the central nervous system. In particular, research featured explores the neuronal response to stress due to excess excitatory stimuli, multiple roles for pres...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.2004456

    authors: Ferrarelli LK,Gough NR

    更新日期:2013-07-09 00:00:00

  • ER stress in pancreatic beta cells: the thin red line between adaptation and failure.

    abstract::Secretory cells, such as pancreatic beta cells, face the challenge of increasing protein synthesis severalfold during acute or chronic stimulation. This poses a burden on the endoplasmic reticulum (ER), the organelle where proinsulin synthesis and folding takes place. Thus, beta cells use various adaptive mechanisms t...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.3110pe7

    authors: Eizirik DL,Cnop M

    更新日期:2010-02-23 00:00:00

  • Lack of the phosphatase PTPN22 increases adhesion of murine regulatory T cells to improve their immunosuppressive function.

    abstract::The cytoplasmic phosphatase PTPN22 (protein tyrosine phosphatase nonreceptor type 22) plays a key role in regulating lymphocyte homeostasis, which ensures that the total number of lymphocytes in the periphery remains relatively constant. Mutations in PTPN22 confer an increased risk of developing autoimmune diseases; h...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2003365

    authors: Brownlie RJ,Miosge LA,Vassilakos D,Svensson LM,Cope A,Zamoyska R

    更新日期:2012-11-27 00:00:00