Quantitative proteomic analyses of dynamic signalling events in cortical neurons undergoing excitotoxic cell death
Excitotoxicity, caused by overstimulation or dysregulation of ionotropic glutamate receptors (iGluRs), is a pathological process directing neuronal death in many neurological disorders. The aberrantly stimulated iGluRs direct massive influx of calcium ions into the affected neurons, leading to chang...
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creator | Hoque, Ashfaqul Williamson, Nicholas A. Ameen, S. Sadia Ciccotosto, Giuseppe D. Hossain, M. Iqbal Oakhill, Jonathan S. Ng, Dominic C. H. Ang, Ching-Seng Cheng, Heung-Chin |
description | Excitotoxicity, caused by overstimulation or dysregulation of ionotropic glutamate receptors (iGluRs), is a pathological process directing neuronal death in many neurological disorders. The aberrantly stimulated iGluRs direct massive influx of calcium ions into the affected neurons, leading to changes in expression and phosphorylation of specific proteins to modulate their functions and direct their participation in the signalling pathways that induce excitotoxic neuronal death. To define these pathways, we used quantitative proteomic approaches to identify these neuronal proteins (referred to as the changed proteins) and determine how their expression and/or phosphorylation dynamically changed in association with excitotoxic cell death. Our data, available in ProteomeXchange with identifier PXD008353, identified over 100 changed proteins exhibiting significant alterations in abundance and/or phosphorylation levels at different time points (5–240 min) in neurons after glutamate overstimulation. Bioinformatic analyses predicted that many of them are components of signalling networks directing defective neuronal morphology and functions. Among them, the well-known neuronal survival regulators including mitogen-activated protein kinases Erk1/2, glycogen synthase kinase 3 (GSK3) and microtubule-associated protein (Tau), were selected for validation by biochemical approaches, which confirmed the findings of the proteomic analysis. Bioinformatic analysis predicted Protein Kinase B (Akt), c-Jun kinase (JNK), cyclin-dependent protein kinase 5 (Cdk5), MAP kinase kinase (MEK), Casein kinase 2 (CK2), Rho-activated protein kinase (Rock) and Serum/glucocorticoid-regulated kinase 1 (SGK1) as the potential upstream kinases phosphorylating some of the changed proteins. Further biochemical investigation confirmed the predictions of sustained changes of the activation states of neuronal Akt and CK2 in excitotoxicity. Thus, future investigation to define the signalling pathways directing the dynamic alterations in abundance and phosphorylation of the identified changed neuronal proteins will help elucidate the molecular mechanism of neuronal death in excitotoxicity. |
doi_str_mv | 10.1038/s41419-019-1445-0 |
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Sadia ; Ciccotosto, Giuseppe D. ; Hossain, M. Iqbal ; Oakhill, Jonathan S. ; Ng, Dominic C. H. ; Ang, Ching-Seng ; Cheng, Heung-Chin</creator><creatorcontrib>Hoque, Ashfaqul ; Williamson, Nicholas A. ; Ameen, S. Sadia ; Ciccotosto, Giuseppe D. ; Hossain, M. Iqbal ; Oakhill, Jonathan S. ; Ng, Dominic C. H. ; Ang, Ching-Seng ; Cheng, Heung-Chin</creatorcontrib><description>Excitotoxicity, caused by overstimulation or dysregulation of ionotropic glutamate receptors (iGluRs), is a pathological process directing neuronal death in many neurological disorders. The aberrantly stimulated iGluRs direct massive influx of calcium ions into the affected neurons, leading to changes in expression and phosphorylation of specific proteins to modulate their functions and direct their participation in the signalling pathways that induce excitotoxic neuronal death. To define these pathways, we used quantitative proteomic approaches to identify these neuronal proteins (referred to as the changed proteins) and determine how their expression and/or phosphorylation dynamically changed in association with excitotoxic cell death. Our data, available in ProteomeXchange with identifier PXD008353, identified over 100 changed proteins exhibiting significant alterations in abundance and/or phosphorylation levels at different time points (5–240 min) in neurons after glutamate overstimulation. Bioinformatic analyses predicted that many of them are components of signalling networks directing defective neuronal morphology and functions. Among them, the well-known neuronal survival regulators including mitogen-activated protein kinases Erk1/2, glycogen synthase kinase 3 (GSK3) and microtubule-associated protein (Tau), were selected for validation by biochemical approaches, which confirmed the findings of the proteomic analysis. Bioinformatic analysis predicted Protein Kinase B (Akt), c-Jun kinase (JNK), cyclin-dependent protein kinase 5 (Cdk5), MAP kinase kinase (MEK), Casein kinase 2 (CK2), Rho-activated protein kinase (Rock) and Serum/glucocorticoid-regulated kinase 1 (SGK1) as the potential upstream kinases phosphorylating some of the changed proteins. Further biochemical investigation confirmed the predictions of sustained changes of the activation states of neuronal Akt and CK2 in excitotoxicity. Thus, future investigation to define the signalling pathways directing the dynamic alterations in abundance and phosphorylation of the identified changed neuronal proteins will help elucidate the molecular mechanism of neuronal death in excitotoxicity.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-019-1445-0</identifier><identifier>PMID: 30824683</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/51 ; 631/378/1934 ; 631/378/340 ; 631/45/475/2290 ; 64 ; 64/60 ; 96 ; 96/106 ; AKT protein ; Animals ; Antibodies ; Apoptosis ; Biochemistry ; Biomedical and Life Sciences ; c-Jun protein ; Calcium influx ; Casein ; Casein kinase II ; Casein Kinase II - chemistry ; Casein Kinase II - genetics ; Casein Kinase II - metabolism ; Cell Biology ; Cell Culture ; Cell Death ; Cell Survival ; Cells, Cultured ; Chromatography, Liquid ; Computational Biology ; Cyclin-dependent kinase 5 ; Excitotoxicity ; Extracellular signal-regulated kinase ; Glucocorticoids ; Glutamic Acid - metabolism ; Glutamic Acid - toxicity ; Glutamic acid receptors (ionotropic) ; Glycogen ; Glycogen synthase kinase 3 ; Glycogen Synthase Kinase 3 - genetics ; Glycogen Synthase Kinase 3 - metabolism ; Immunology ; Kinases ; Life Sciences ; MAP kinase ; MAP kinase kinase ; Mice ; Mitogen-Activated Protein Kinase 1 - chemistry ; Mitogen-Activated Protein Kinase 1 - genetics ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 3 - chemistry ; Mitogen-Activated Protein Kinase 3 - genetics ; Mitogen-Activated Protein Kinase 3 - metabolism ; Nerve Tissue Proteins - chemistry ; Nerve Tissue Proteins - metabolism ; Neurological diseases ; Neurons - cytology ; Neurons - drug effects ; Neurons - metabolism ; Neurons - pathology ; Phosphorylation ; Proteins ; Proteomics ; Proto-Oncogene Proteins c-akt - genetics ; Proto-Oncogene Proteins c-akt - metabolism ; Receptor, trkA - genetics ; Receptor, trkA - metabolism ; Signal transduction ; Signal Transduction - drug effects ; Signal Transduction - genetics ; Software ; Tandem Mass Spectrometry ; Tau protein ; tau Proteins - chemistry ; tau Proteins - genetics ; tau Proteins - metabolism ; Transcription factors</subject><ispartof>Cell death & disease, 2019-03, Vol.10 (3), p.213-213, Article 213</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-db0f9569fd471ed54f7167499c11b42ea58e6515df93d87f98ec59e87dd858b13</citedby><cites>FETCH-LOGICAL-c470t-db0f9569fd471ed54f7167499c11b42ea58e6515df93d87f98ec59e87dd858b13</cites><orcidid>0000-0002-9475-1440 ; 0000-0002-2173-3452 ; 0000-0003-2384-2983 ; 0000-0002-4965-7148</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397184/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397184/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30824683$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hoque, Ashfaqul</creatorcontrib><creatorcontrib>Williamson, Nicholas A.</creatorcontrib><creatorcontrib>Ameen, S. Sadia</creatorcontrib><creatorcontrib>Ciccotosto, Giuseppe D.</creatorcontrib><creatorcontrib>Hossain, M. Iqbal</creatorcontrib><creatorcontrib>Oakhill, Jonathan S.</creatorcontrib><creatorcontrib>Ng, Dominic C. H.</creatorcontrib><creatorcontrib>Ang, Ching-Seng</creatorcontrib><creatorcontrib>Cheng, Heung-Chin</creatorcontrib><title>Quantitative proteomic analyses of dynamic signalling events in cortical neurons undergoing excitotoxic cell death</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>Excitotoxicity, caused by overstimulation or dysregulation of ionotropic glutamate receptors (iGluRs), is a pathological process directing neuronal death in many neurological disorders. The aberrantly stimulated iGluRs direct massive influx of calcium ions into the affected neurons, leading to changes in expression and phosphorylation of specific proteins to modulate their functions and direct their participation in the signalling pathways that induce excitotoxic neuronal death. To define these pathways, we used quantitative proteomic approaches to identify these neuronal proteins (referred to as the changed proteins) and determine how their expression and/or phosphorylation dynamically changed in association with excitotoxic cell death. Our data, available in ProteomeXchange with identifier PXD008353, identified over 100 changed proteins exhibiting significant alterations in abundance and/or phosphorylation levels at different time points (5–240 min) in neurons after glutamate overstimulation. Bioinformatic analyses predicted that many of them are components of signalling networks directing defective neuronal morphology and functions. Among them, the well-known neuronal survival regulators including mitogen-activated protein kinases Erk1/2, glycogen synthase kinase 3 (GSK3) and microtubule-associated protein (Tau), were selected for validation by biochemical approaches, which confirmed the findings of the proteomic analysis. Bioinformatic analysis predicted Protein Kinase B (Akt), c-Jun kinase (JNK), cyclin-dependent protein kinase 5 (Cdk5), MAP kinase kinase (MEK), Casein kinase 2 (CK2), Rho-activated protein kinase (Rock) and Serum/glucocorticoid-regulated kinase 1 (SGK1) as the potential upstream kinases phosphorylating some of the changed proteins. Further biochemical investigation confirmed the predictions of sustained changes of the activation states of neuronal Akt and CK2 in excitotoxicity. Thus, future investigation to define the signalling pathways directing the dynamic alterations in abundance and phosphorylation of the identified changed neuronal proteins will help elucidate the molecular mechanism of neuronal death in excitotoxicity.</description><subject>13</subject><subject>13/51</subject><subject>631/378/1934</subject><subject>631/378/340</subject><subject>631/45/475/2290</subject><subject>64</subject><subject>64/60</subject><subject>96</subject><subject>96/106</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>c-Jun protein</subject><subject>Calcium influx</subject><subject>Casein</subject><subject>Casein kinase II</subject><subject>Casein Kinase II - chemistry</subject><subject>Casein Kinase II - genetics</subject><subject>Casein Kinase II - metabolism</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell Death</subject><subject>Cell Survival</subject><subject>Cells, Cultured</subject><subject>Chromatography, Liquid</subject><subject>Computational Biology</subject><subject>Cyclin-dependent kinase 5</subject><subject>Excitotoxicity</subject><subject>Extracellular signal-regulated kinase</subject><subject>Glucocorticoids</subject><subject>Glutamic Acid - metabolism</subject><subject>Glutamic Acid - toxicity</subject><subject>Glutamic acid receptors (ionotropic)</subject><subject>Glycogen</subject><subject>Glycogen synthase kinase 3</subject><subject>Glycogen Synthase Kinase 3 - genetics</subject><subject>Glycogen Synthase Kinase 3 - metabolism</subject><subject>Immunology</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>MAP kinase</subject><subject>MAP kinase kinase</subject><subject>Mice</subject><subject>Mitogen-Activated Protein Kinase 1 - chemistry</subject><subject>Mitogen-Activated Protein Kinase 1 - genetics</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3 - chemistry</subject><subject>Mitogen-Activated Protein Kinase 3 - genetics</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Nerve Tissue Proteins - chemistry</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Neurological diseases</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptor, trkA - genetics</subject><subject>Receptor, trkA - metabolism</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - genetics</subject><subject>Software</subject><subject>Tandem Mass Spectrometry</subject><subject>Tau protein</subject><subject>tau Proteins - chemistry</subject><subject>tau Proteins - genetics</subject><subject>tau Proteins - metabolism</subject><subject>Transcription factors</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kdFqHSEQhqU0NCHNA_SmCL3pzaa66q7eFEpom0KgFJJr8ejsxrBHT9U95Lx93W6SpoUKosx88zvjj9AbSs4pYfJD5pRT1ZC6KeeiIS_QSUs4bbiU6uWz-zE6y_mO1MUYaUX3Ch0zIlveSXaC0o_ZhOKLKX4PeJdigbj1FptgpkOGjOOA3SGYJZb9WKOTDyOGPYSSsQ_YxlS8NRMOMKcYMp6DgzTG39S99SWWeF-LLUwTdmDK7Wt0NJgpw9nDeYpuvny-vrhsrr5__Xbx6aqxvCelcRsyKNGpwfGeghN86GnXc6UspRveghESOkGFGxRzsh-UBCsUyN45KeSGslP0cdXdzZstOFs7TmbSu-S3Jh10NF7_nQn-Vo9xrzumeip5FXj_IJDizxly0VuflzlMgDhn3VLZC0ZEu6Dv_kHv4pzqb60UFYJyWSm6UjbFnBMMT81QohdT9WqqrqbqxVRNas3b51M8VTxaWIF2BXJNhRHSn6f_r_oLsMGvww</recordid><startdate>20190301</startdate><enddate>20190301</enddate><creator>Hoque, Ashfaqul</creator><creator>Williamson, Nicholas A.</creator><creator>Ameen, S. 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Sadia ; Ciccotosto, Giuseppe D. ; Hossain, M. Iqbal ; Oakhill, Jonathan S. ; Ng, Dominic C. H. ; Ang, Ching-Seng ; Cheng, Heung-Chin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-db0f9569fd471ed54f7167499c11b42ea58e6515df93d87f98ec59e87dd858b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>13</topic><topic>13/51</topic><topic>631/378/1934</topic><topic>631/378/340</topic><topic>631/45/475/2290</topic><topic>64</topic><topic>64/60</topic><topic>96</topic><topic>96/106</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>c-Jun protein</topic><topic>Calcium influx</topic><topic>Casein</topic><topic>Casein kinase II</topic><topic>Casein Kinase II - chemistry</topic><topic>Casein Kinase II - genetics</topic><topic>Casein Kinase II - metabolism</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell Death</topic><topic>Cell Survival</topic><topic>Cells, Cultured</topic><topic>Chromatography, Liquid</topic><topic>Computational Biology</topic><topic>Cyclin-dependent kinase 5</topic><topic>Excitotoxicity</topic><topic>Extracellular signal-regulated kinase</topic><topic>Glucocorticoids</topic><topic>Glutamic Acid - metabolism</topic><topic>Glutamic Acid - toxicity</topic><topic>Glutamic acid receptors (ionotropic)</topic><topic>Glycogen</topic><topic>Glycogen synthase kinase 3</topic><topic>Glycogen Synthase Kinase 3 - genetics</topic><topic>Glycogen Synthase Kinase 3 - metabolism</topic><topic>Immunology</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>MAP kinase</topic><topic>MAP kinase kinase</topic><topic>Mice</topic><topic>Mitogen-Activated Protein Kinase 1 - chemistry</topic><topic>Mitogen-Activated Protein Kinase 1 - genetics</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Mitogen-Activated Protein Kinase 3 - chemistry</topic><topic>Mitogen-Activated Protein Kinase 3 - genetics</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Nerve Tissue Proteins - chemistry</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Neurological diseases</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neurons - pathology</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Receptor, trkA - genetics</topic><topic>Receptor, trkA - metabolism</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - genetics</topic><topic>Software</topic><topic>Tandem Mass Spectrometry</topic><topic>Tau protein</topic><topic>tau Proteins - chemistry</topic><topic>tau Proteins - genetics</topic><topic>tau Proteins - metabolism</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hoque, Ashfaqul</creatorcontrib><creatorcontrib>Williamson, Nicholas A.</creatorcontrib><creatorcontrib>Ameen, S. 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Sadia</au><au>Ciccotosto, Giuseppe D.</au><au>Hossain, M. Iqbal</au><au>Oakhill, Jonathan S.</au><au>Ng, Dominic C. H.</au><au>Ang, Ching-Seng</au><au>Cheng, Heung-Chin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantitative proteomic analyses of dynamic signalling events in cortical neurons undergoing excitotoxic cell death</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2019-03-01</date><risdate>2019</risdate><volume>10</volume><issue>3</issue><spage>213</spage><epage>213</epage><pages>213-213</pages><artnum>213</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>Excitotoxicity, caused by overstimulation or dysregulation of ionotropic glutamate receptors (iGluRs), is a pathological process directing neuronal death in many neurological disorders. The aberrantly stimulated iGluRs direct massive influx of calcium ions into the affected neurons, leading to changes in expression and phosphorylation of specific proteins to modulate their functions and direct their participation in the signalling pathways that induce excitotoxic neuronal death. To define these pathways, we used quantitative proteomic approaches to identify these neuronal proteins (referred to as the changed proteins) and determine how their expression and/or phosphorylation dynamically changed in association with excitotoxic cell death. Our data, available in ProteomeXchange with identifier PXD008353, identified over 100 changed proteins exhibiting significant alterations in abundance and/or phosphorylation levels at different time points (5–240 min) in neurons after glutamate overstimulation. Bioinformatic analyses predicted that many of them are components of signalling networks directing defective neuronal morphology and functions. Among them, the well-known neuronal survival regulators including mitogen-activated protein kinases Erk1/2, glycogen synthase kinase 3 (GSK3) and microtubule-associated protein (Tau), were selected for validation by biochemical approaches, which confirmed the findings of the proteomic analysis. Bioinformatic analysis predicted Protein Kinase B (Akt), c-Jun kinase (JNK), cyclin-dependent protein kinase 5 (Cdk5), MAP kinase kinase (MEK), Casein kinase 2 (CK2), Rho-activated protein kinase (Rock) and Serum/glucocorticoid-regulated kinase 1 (SGK1) as the potential upstream kinases phosphorylating some of the changed proteins. Further biochemical investigation confirmed the predictions of sustained changes of the activation states of neuronal Akt and CK2 in excitotoxicity. Thus, future investigation to define the signalling pathways directing the dynamic alterations in abundance and phosphorylation of the identified changed neuronal proteins will help elucidate the molecular mechanism of neuronal death in excitotoxicity.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30824683</pmid><doi>10.1038/s41419-019-1445-0</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-9475-1440</orcidid><orcidid>https://orcid.org/0000-0002-2173-3452</orcidid><orcidid>https://orcid.org/0000-0003-2384-2983</orcidid><orcidid>https://orcid.org/0000-0002-4965-7148</orcidid><oa>free_for_read</oa></addata></record> |
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issn | 2041-4889 2041-4889 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6397184 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central |
subjects | 13 13/51 631/378/1934 631/378/340 631/45/475/2290 64 64/60 96 96/106 AKT protein Animals Antibodies Apoptosis Biochemistry Biomedical and Life Sciences c-Jun protein Calcium influx Casein Casein kinase II Casein Kinase II - chemistry Casein Kinase II - genetics Casein Kinase II - metabolism Cell Biology Cell Culture Cell Death Cell Survival Cells, Cultured Chromatography, Liquid Computational Biology Cyclin-dependent kinase 5 Excitotoxicity Extracellular signal-regulated kinase Glucocorticoids Glutamic Acid - metabolism Glutamic Acid - toxicity Glutamic acid receptors (ionotropic) Glycogen Glycogen synthase kinase 3 Glycogen Synthase Kinase 3 - genetics Glycogen Synthase Kinase 3 - metabolism Immunology Kinases Life Sciences MAP kinase MAP kinase kinase Mice Mitogen-Activated Protein Kinase 1 - chemistry Mitogen-Activated Protein Kinase 1 - genetics Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - chemistry Mitogen-Activated Protein Kinase 3 - genetics Mitogen-Activated Protein Kinase 3 - metabolism Nerve Tissue Proteins - chemistry Nerve Tissue Proteins - metabolism Neurological diseases Neurons - cytology Neurons - drug effects Neurons - metabolism Neurons - pathology Phosphorylation Proteins Proteomics Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Receptor, trkA - genetics Receptor, trkA - metabolism Signal transduction Signal Transduction - drug effects Signal Transduction - genetics Software Tandem Mass Spectrometry Tau protein tau Proteins - chemistry tau Proteins - genetics tau Proteins - metabolism Transcription factors |
title | Quantitative proteomic analyses of dynamic signalling events in cortical neurons undergoing excitotoxic cell death |
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