当前位置： SCI文献检索 > Science Signaling期刊下所有文献 > Aβ oligomers induce pathophysiological mGluR5 signaling in Alzheimer's disease model mice in a sex-selective manner.

Aβ oligomers induce pathophysiological mGluR5 signaling in Alzheimer's disease model mice in a sex-selective manner.

Abstract：

:The prevalence, presentation, and progression of Alzheimer's disease (AD) differ between men and women, although β-amyloid (Aβ) deposition is a pathological hallmark of AD in both sexes. Aβ-induced activation of the neuronal glutamate receptor mGluR5 is linked to AD progression. However, we found that mGluR5 exhibits distinct sex-dependent profiles. Specifically, mGluR5 isolated from male mouse cortical and hippocampal tissues bound with high affinity to Aβ oligomers, whereas mGluR5 from female mice exhibited no such affinity. This sex-selective Aβ-mGluR5 interaction did not appear to depend on estrogen, but rather Aβ interaction with cellular prion protein (PrPC), which was detected only in male mouse brain homogenates. The ternary complex between mGluR5, Aβ oligomers, and PrPC was essential to elicit mGluR5-dependent pathological suppression of autophagy in primary neuronal cultures. Pharmacological inhibition of mGluR5 reactivated autophagy, mitigated Aβ pathology, and reversed cognitive decline in male APPswe/PS1ΔE9 mice, but not in their female counterparts. Aβ oligomers also bound with high affinity to human mGluR5 isolated from postmortem donor male cortical brain tissue, but not that from female samples, suggesting that this mechanism may be relevant to patients. Our findings indicate that mGluR5 does not contribute to Aβ pathology in females, highlighting the complexity of mGluR5 pharmacology and Aβ signaling that supports the need for sex-specific stratification in clinical trials assessing AD therapeutics.

journal_name

Sci Signal

journal_title

Science signaling

authors

Abd-Elrahman KS,Albaker A,de Souza JM,Ribeiro FM,Schlossmacher MG,Tiberi M,Hamilton A,Ferguson SSG

doi

10.1126/scisignal.abd2494

subject

Has Abstract

pub_date

2020-12-15 00:00:00

issue

662

eissn

1945-0877

issn

1937-9145

pii

13/662/eabd2494

journal_volume

13

pub_type

杂志文章

相关文献

Science Signaling文献大全
  • Dysregulation of microRNA biogenesis and gene silencing in cancer.

    abstract：:MicroRNAs (miRNAs) are small noncoding RNAs that suppress the abundance of partially complementary mRNAs and inhibit their translation. Each miRNA can regulate hundreds of mRNAs, sometimes strongly but often weakly, to mediate a diverse array of biological functions, including proliferation, cell signaling, differenti...

    journal_title：Science signaling

    pub_type： 杂志文章,评审

    doi：10.1126/scisignal.2005825

    authors： Hata A,Lieberman J

    更新日期：2015-03-17 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

  • STIM2 enhances receptor-stimulated Ca²⁺ signaling by promoting recruitment of STIM1 to the endoplasmic reticulum-plasma membrane junctions.

    abstract：:A central component of receptor-evoked Ca(2+) signaling is store-operated Ca(2+) entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response to depletion of ER Ca(2+). We report that STIM2 enhances agonist-mediated activa...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2005748

    authors： Ong HL,de Souza LB,Zheng C,Cheng KT,Liu X,Goldsmith CM,Feske S,Ambudkar IS

    更新日期：2015-01-13 00:00:00

  • AKAP150-dependent cooperative TRPV4 channel gating is central to endothelium-dependent vasodilation and is disrupted in hypertension.

    abstract：:Endothelial cell dysfunction, characterized by a diminished response to endothelial cell-dependent vasodilators, is a hallmark of hypertension. TRPV4 channels play a major role in endothelial-dependent vasodilation, a function mediated by local Ca(2+) influx through clusters of functionally coupled TRPV4 channels rath...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2005052

    authors： Sonkusare SK,Dalsgaard T,Bonev AD,Hill-Eubanks DC,Kotlikoff MI,Scott JD,Santana LF,Nelson MT

    更新日期：2014-07-08 00:00:00

  • Receptor cooperation in B cells.

    abstract：:TLR4-stimulated B cell activation is mediated by the tyrosine kinase Syk and depends on the B cell receptor. ...

    journal_title：Science signaling

    pub_type： 评论,杂志文章

    doi：10.1126/scisignal.aan7951

    authors： Foley JF

    更新日期：2017-05-23 00:00:00

  • Acetylation goes global: the emergence of acetylation biology.

    abstract：:For the first 30 years since its discovery, reversible protein acetylation has been studied and understood almost exclusively in the context of histone modification and gene transcription. With the discovery of non-histone acetylated proteins and acetylation-modifying enzymes in cellular compartments outside the nucle...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.297pe76

    authors： Norris KL,Lee JY,Yao TP

    更新日期：2009-11-17 00:00:00

  • Transforming growth factor-β and Notch ligands act as opposing environmental cues in regulating the plasticity of type 3 innate lymphoid cells.

    abstract：:Group 3 innate lymphoid cells (ILC3s) are composed of subsets that are either positive or negative for the natural cytotoxicity receptor (NCR) NKp46 (encoded by Ncr1). ILC3s are located at mucosal sites, such as in the intestine and lung, where they are exposed to billions of commensal microbes and potentially harmful...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aaf2176

    authors： Viant C,Rankin LC,Girard-Madoux MJ,Seillet C,Shi W,Smyth MJ,Bartholin L,Walzer T,Huntington ND,Vivier E,Belz GT

    更新日期：2016-05-03 00:00:00

  • Gain-of-function mutations in protein kinase Cα (PKCα) may promote synaptic defects in Alzheimer's disease.

    abstract：:Alzheimer's disease (AD) is a progressive dementia disorder characterized by synaptic degeneration and amyloid-β (Aβ) accumulation in the brain. Through whole-genome sequencing of 1345 individuals from 410 families with late-onset AD (LOAD), we identified three highly penetrant variants in PRKCA, the gene that encodes...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aaf6209

    authors： Alfonso SI,Callender JA,Hooli B,Antal CE,Mullin K,Sherman MA,Lesné SE,Leitges M,Newton AC,Tanzi RE,Malinow R

    更新日期：2016-05-10 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

  • Tumors block pain with CXCL12.

    abstract：:The chemokine CXCL12 released from early stage pancreatic cancer recruits Schwann cells and suppresses pain signaling. ...

    journal_title：Science signaling

    pub_type： 评论,杂志文章

    doi：10.1126/scisignal.aam7233

    authors： Gough NR

    更新日期：2017-01-10 00:00:00

  • The STING in the tail for cytosolic DNA-dependent activation of IRF3.

    abstract：:Cytosolic pattern recognition receptors (PRRs) sense intracellular nucleic acids from pathogens such as bacteria and viruses, which leads to the induction of type I interferon (IFN) responses that are essential for an effective immune response. Further, these PRR pathways can be aberrantly activated by self DNA, which...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2002919

    authors： Bowie A

    更新日期：2012-03-06 00:00:00

  • Convergence of Wnt, growth factor, and heterotrimeric G protein signals on the guanine nucleotide exchange factor Daple.

    abstract：:Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades, and their dysregulation plays an integral role in cancer progression. Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor ty...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aao4220

    authors： Aznar N,Ear J,Dunkel Y,Sun N,Satterfield K,He F,Kalogriopoulos NA,Lopez-Sanchez I,Ghassemian M,Sahoo D,Kufareva I,Ghosh P

    更新日期：2018-02-27 00:00:00

  • The costimulatory molecule CD226 signals through VAV1 to amplify TCR signals and promote IL-17 production by CD4+ T cells.

    abstract：:The activation of T cells requires the guanine nucleotide exchange factor VAV1. Using mice in which a tag for affinity purification was attached to endogenous VAV1 molecules, we analyzed by quantitative mass spectrometry the signaling complex that assembles around activated VAV1. Fifty VAV1-binding partners were ident...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aar3083

    authors： Gaud G,Roncagalli R,Chaoui K,Bernard I,Familiades J,Colacios C,Kassem S,Monsarrat B,Burlet-Schiltz O,de Peredo AG,Malissen B,Saoudi A

    更新日期：2018-07-10 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

  • cAMPr: A single-wavelength fluorescent sensor for cyclic AMP.

    abstract：:Genetically encoded fluorescent sensors enable cell-specific measurements of ions and small molecules in real time. Cyclic adenosine monophosphate (cAMP) is one of the most important signaling molecules in virtually all cell types and organisms. We describe cAMPr, a new single-wavelength cAMP sensor. We developed cAMP...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aah3738

    authors： Hackley CR,Mazzoni EO,Blau J

    更新日期：2018-03-06 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

  • Arabidopsis jasmonate signaling pathway.

    abstract：:Jasmonates control defense gene expression, growth, and fertility throughout the plant kingdom and have been studied extensively in Arabidopsis thaliana. The prohormone jasmonic acid (JA) is conjugated to amino acids such as isoleucine to form the active hormone jasmonoyl-isoleucine (JA-Ile). A series of breakthroughs...

    journal_title：Science signaling

    pub_type： 杂志文章,评审

    doi：10.1126/scisignal.3109cm4

    authors： Gfeller A,Liechti R,Farmer EE

    更新日期：2010-02-16 00:00:00

  • Receptor tyrosine kinases fall into distinct classes based on their inferred signaling networks.

    abstract：:Although many anticancer drugs that target receptor tyrosine kinases (RTKs) provide clinical benefit, their long-term use is limited by resistance that is often attributed to increased abundance or activation of another RTK that compensates for the inhibited receptor. To uncover common and unique features in the signa...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2003994

    authors： Wagner JP,Wolf-Yadlin A,Sevecka M,Grenier JK,Root DE,Lauffenburger DA,MacBeath G

    更新日期：2013-07-16 00:00:00

  • The endothelial adaptor molecule TSAd is required for VEGF-induced angiogenic sprouting through junctional c-Src activation.

    abstract：:Activation of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) by VEGF binding is critical for vascular morphogenesis. In addition, VEGF disrupts the endothelial barrier by triggering the phosphorylation and turnover of the junctional molecule VE-cadherin, a process mediated by the VEGFR2 downstream effec...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aad9256

    authors： Gordon EJ,Fukuhara D,Weström S,Padhan N,Sjöström EO,van Meeteren L,He L,Orsenigo F,Dejana E,Bentley K,Spurkland A,Claesson-Welsh L

    更新日期：2016-07-19 00:00:00

  • Neratinib is effective in breast tumors bearing both amplification and mutation of ERBB2 (HER2).

    abstract：:Mutations in ERBB2, the gene encoding epidermal growth factor receptor (EGFR) family member HER2, are common in and drive the growth of "HER2-negative" (not ERBB2 amplified) tumors but are rare in "HER2-positive" (ERBB2 amplified) breast cancer. We analyzed DNA-sequencing data from HER2-positive patients and used cell...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aat9773

    authors： Cocco E,Javier Carmona F,Razavi P,Won HH,Cai Y,Rossi V,Chan C,Cownie J,Soong J,Toska E,Shifman SG,Sarotto I,Savas P,Wick MJ,Papadopoulos KP,Moriarty A,Cutler RE Jr,Avogadri-Connors F,Lalani AS,Bryce RP,Chandarlapa

    更新日期：2018-10-09 00:00:00

  • Innate immune memory and homeostasis may be conferred through crosstalk between the TLR3 and TLR7 pathways.

    abstract：:Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate the innate immune response through the production of cytokines. The innate immune response depends on the timing of encountering PAMPs, suggesting a short-term "memory." In particular, activation of TLR3 appears to prime ...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aac9340

    authors： Liu B,Liu Q,Yang L,Palaniappan SK,Bahar I,Thiagarajan PS,Ding JL

    更新日期：2016-07-12 00:00:00

  • Cycles of ubiquitination and deubiquitination critically regulate growth factor-mediated activation of Akt signaling.

    abstract：:K63-linked ubiquitination of Akt is a posttranslational modification that plays a critical role in growth factor-mediated membrane recruitment and activation of Akt. Although E3 ligases involved in growth factor-induced ubiquitination of Akt have been defined, the deubiquitinating enzyme (DUB) that triggers deubiquiti...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2003197

    authors： Yang WL,Jin G,Li CF,Jeong YS,Moten A,Xu D,Feng Z,Chen W,Cai Z,Darnay B,Gu W,Lin HK

    更新日期：2013-01-08 00:00:00

  • The early synthesis of p35 and activation of CDK5 in LPS-stimulated macrophages suppresses interleukin-10 production.

    abstract：:Interleukin-10 (IL-10) is an important anti-inflammatory cytokine that is produced primarily by macrophages. We investigated mechanisms by which the timing of IL-10 production was controlled in macrophages and found that cyclin-dependent kinase 5 (CDK5) activity was markedly increased in lipopolysaccharide (LPS)-stimu...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aab3156

    authors： Na YR,Jung D,Gu GJ,Jang AR,Suh YH,Seok SH

    更新日期：2015-11-24 00:00:00

  • Inhibition of the kinase ITK in a mouse model of asthma reduces cell death and fails to inhibit the inflammatory response.

    abstract：:Interleukin-2 (IL-2)-inducible T cell kinase (ITK) mediates T cell receptor (TCR) signaling primarily to stimulate the production of cytokines, such as IL-4, IL-5, and IL-13, from T helper 2 (TH2) cells. Compared to wild-type mice, ITK knockout mice are resistant to asthma and exhibit reduced lung inflammation and dec...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aab0949

    authors： Sun Y,Peng I,Webster JD,Suto E,Lesch J,Wu X,Senger K,Francis G,Barrett K,Collier JL,Burch JD,Zhou M,Chen Y,Chan C,Eastham-Anderson J,Ngu H,Li O,Staton T,Havnar C,Jaochico A,Jackman J,Jeet S,Riol-Blanco L,Wu

    更新日期：2015-12-01 00:00:00

  • Genome to kinome: species-specific peptide arrays for kinome analysis.

    abstract：:Tools for conducting high-throughput kinome analysis do not exist for many species. For example, two commonly used techniques for monitoring phosphorylation events are phosphorylation-specific antibodies and peptide arrays. The majority of phosphorylation-specific antibodies are for human or mouse targets, and the con...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.254pl1

    authors： Jalal S,Arsenault R,Potter AA,Babiuk LA,Griebel PJ,Napper S

    更新日期：2009-01-20 00:00:00

  • Educated natural killer cells show dynamic movement of the activating receptor NKp46 and confinement of the inhibitory receptor Ly49A.

    abstract：:Educated natural killer (NK) cells have inhibitory receptors specific for self major histocompatibility complex (MHC) class I molecules and kill cancer cells more efficiently than do NK cells that do not have such receptors (hyporesponsive NK cells). The mechanism behind this functional empowerment through education h...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aai9200

    authors： Staaf E,Hedde PN,Bagawath Singh S,Piguet J,Gratton E,Johansson S

    更新日期：2018-02-13 00:00:00

  • Lgl reduces endosomal vesicle acidification and Notch signaling by promoting the interaction between Vap33 and the V-ATPase complex.

    abstract：:Epithelial cell polarity is linked to the control of tissue growth and tumorigenesis. The tumor suppressor and cell polarity protein lethal-2-giant larvae (Lgl) promotes Hippo signaling and inhibits Notch signaling to restrict tissue growth in Drosophila melanogaster Notch signaling is greater in lgl mutant tissue tha...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.aar1976

    authors： Portela M,Yang L,Paul S,Li X,Veraksa A,Parsons LM,Richardson HE

    更新日期：2018-06-05 00:00:00

  • Controlling long-term signaling: receptor dynamics determine attenuation and refractory behavior of the TGF-β pathway.

    abstract：:Understanding the complex dynamics of growth factor signaling requires both mechanistic and kinetic information. Although signaling dynamics have been studied for pathways downstream of receptor tyrosine kinases and G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors, they have not been inv...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2004416

    authors： Vizán P,Miller DS,Gori I,Das D,Schmierer B,Hill CS

    更新日期：2013-12-10 00:00:00

  • FOXP1 potentiates Wnt/β-catenin signaling in diffuse large B cell lymphoma.

    abstract：:The transcription factor FOXP1 (forkhead box protein P1) is a master regulator of stem and progenitor cell biology. In diffuse large B cell lymphoma (DLBCL), copy number amplifications and chromosomal translocations result in overexpression of FOXP1. Increased abundance of FOXP1 in DLBCL is a predictor of poor prognos...

    journal_title：Science signaling

    pub_type： 杂志文章

    doi：10.1126/scisignal.2005654

    authors： Walker MP,Stopford CM,Cederlund M,Fang F,Jahn C,Rabinowitz AD,Goldfarb D,Graham DM,Yan F,Deal AM,Fedoriw Y,Richards KL,Davis IJ,Weidinger G,Damania B,Major MB

    更新日期：2015-02-03 00:00:00

  • 2015: Signaling Breakthroughs of the Year.

    abstract：:This year's signaling breakthroughs highlight insights into the pathogenesis or treatment of cancer, malaria, and neurodegenerative disorders; reveal molecular insights into cell death; and identify signals that could be leveraged to prevent plant parasitism or engineer bacteria as microbial fuel cells. ...

    journal_title：Science signaling

    pub_type： 社论

    doi：10.1126/scisignal.aad9795

    authors： Adler EM

    更新日期：2016-01-05 00:00:00