Roles of the Akt/GSK-3 and Wnt Signaling Pathways in Schizophrenia and Antipsychotic Drug Action
AbstractDopamine D2 receptor antagonism is a unifying property of all antipsychotic drugs in clinical use. Remarkably, the effector molecules through which these medications exert their actions remain poorly characterized. Increasing attention is being focused on Akt/glycogen synthase kinase-3 (GSK-...
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| Veröffentlicht in: | American Journal of Psychiatry 2010-04, Vol.167 (4), p.388-396 |
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| creator | Freyberg, Zachary Ferrando, Stephen J Javitch, Jonathan A |
| description | AbstractDopamine D2 receptor antagonism is a unifying property of all antipsychotic drugs in clinical use. Remarkably, the effector molecules through which these medications exert their actions remain poorly characterized. Increasing attention is being focused on Akt/glycogen synthase kinase-3 (GSK-3) and wingless (Wnt) signaling pathways, which have been associated with schizophrenia in a number of genetic and postmortem studies. Antipsychotic medications may treat symptoms of psychosis, at least in part, through modulation of levels and activity of Akt, GSK-3, and Wnt-related intracellular signaling. The authors review evidence that Akt/GSK-3 and Wnt-related pathways are involved in the pathogenesis of schizophrenia as well as details of intracellular events related to these molecules mediated by both typical and atypical antipsychotic medications. Further study of Akt/GSK-3 and Wnt signaling may ultimately lead to alternative therapeutics of schizophrenia-related disorders. |
| doi_str_mv | 10.1176/appi.ajp.2009.08121873 |
| format | Article |
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Remarkably, the effector molecules through which these medications exert their actions remain poorly characterized. Increasing attention is being focused on Akt/glycogen synthase kinase-3 (GSK-3) and wingless (Wnt) signaling pathways, which have been associated with schizophrenia in a number of genetic and postmortem studies. Antipsychotic medications may treat symptoms of psychosis, at least in part, through modulation of levels and activity of Akt, GSK-3, and Wnt-related intracellular signaling. The authors review evidence that Akt/GSK-3 and Wnt-related pathways are involved in the pathogenesis of schizophrenia as well as details of intracellular events related to these molecules mediated by both typical and atypical antipsychotic medications. Further study of Akt/GSK-3 and Wnt signaling may ultimately lead to alternative therapeutics of schizophrenia-related disorders.</description><identifier>ISSN: 0002-953X</identifier><identifier>EISSN: 1535-7228</identifier><identifier>DOI: 10.1176/appi.ajp.2009.08121873</identifier><identifier>PMID: 19917593</identifier><identifier>CODEN: AJPSAO</identifier><language>eng</language><publisher>Arlington, VA: American Psychiatric Association</publisher><subject>Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Adaptor Proteins, Signal Transducing - physiology ; Adult and adolescent clinical studies ; Antipsychotic Agents - pharmacology ; Antipsychotic Agents - therapeutic use ; Apoptosis ; Apoptosis Regulatory Proteins - genetics ; Apoptosis Regulatory Proteins - metabolism ; Apoptosis Regulatory Proteins - physiology ; Arrestins - antagonists & inhibitors ; beta Catenin - antagonists & inhibitors ; Biological and medical sciences ; Drugs ; Glycogen Synthase Kinase 3 - genetics ; Glycogen Synthase Kinase 3 - metabolism ; Glycogen Synthase Kinase 3 - physiology ; Humans ; Kinases ; Medical sciences ; Metabolic syndrome ; Metabolism ; Neuropharmacology ; Pharmacology. Drug treatments ; Protein Isoforms ; Proteins ; Psycholeptics: tranquillizer, neuroleptic ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychopharmacology ; Psychoses ; Psychotropic drugs ; Rodents ; Schizophrenia ; Schizophrenia - drug therapy ; Schizophrenia - genetics ; Signal Transduction - drug effects ; Wnt Proteins - genetics</subject><ispartof>American Journal of Psychiatry, 2010-04, Vol.167 (4), p.388-396</ispartof><rights>Copyright © American Psychiatric Association</rights><rights>2015 INIST-CNRS</rights><rights>Copyright American Psychiatric Association Apr 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a580t-694cc5792351bc8c7e5de621f3edd37f871173d8b67e3c346e74ca8a0e0df1e73</citedby><cites>FETCH-LOGICAL-a580t-694cc5792351bc8c7e5de621f3edd37f871173d8b67e3c346e74ca8a0e0df1e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://psychiatryonline.org/doi/epdf/10.1176/appi.ajp.2009.08121873$$EPDF$$P50$$Gappi$$H</linktopdf><linktohtml>$$Uhttps://psychiatryonline.org/doi/full/10.1176/appi.ajp.2009.08121873$$EHTML$$P50$$Gappi$$H</linktohtml><link.rule.ids>230,314,776,780,881,2842,21605,21606,21607,27901,27902,77763,77768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22752409$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19917593$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Freyberg, Zachary</creatorcontrib><creatorcontrib>Ferrando, Stephen J</creatorcontrib><creatorcontrib>Javitch, Jonathan A</creatorcontrib><title>Roles of the Akt/GSK-3 and Wnt Signaling Pathways in Schizophrenia and Antipsychotic Drug Action</title><title>American Journal of Psychiatry</title><addtitle>Am J Psychiatry</addtitle><description>AbstractDopamine D2 receptor antagonism is a unifying property of all antipsychotic drugs in clinical use. Remarkably, the effector molecules through which these medications exert their actions remain poorly characterized. Increasing attention is being focused on Akt/glycogen synthase kinase-3 (GSK-3) and wingless (Wnt) signaling pathways, which have been associated with schizophrenia in a number of genetic and postmortem studies. Antipsychotic medications may treat symptoms of psychosis, at least in part, through modulation of levels and activity of Akt, GSK-3, and Wnt-related intracellular signaling. The authors review evidence that Akt/GSK-3 and Wnt-related pathways are involved in the pathogenesis of schizophrenia as well as details of intracellular events related to these molecules mediated by both typical and atypical antipsychotic medications. Further study of Akt/GSK-3 and Wnt signaling may ultimately lead to alternative therapeutics of schizophrenia-related disorders.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Adaptor Proteins, Signal Transducing - physiology</subject><subject>Adult and adolescent clinical studies</subject><subject>Antipsychotic Agents - pharmacology</subject><subject>Antipsychotic Agents - therapeutic use</subject><subject>Apoptosis</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Apoptosis Regulatory Proteins - physiology</subject><subject>Arrestins - antagonists & inhibitors</subject><subject>beta Catenin - antagonists & inhibitors</subject><subject>Biological and medical sciences</subject><subject>Drugs</subject><subject>Glycogen Synthase Kinase 3 - genetics</subject><subject>Glycogen Synthase Kinase 3 - metabolism</subject><subject>Glycogen Synthase Kinase 3 - physiology</subject><subject>Humans</subject><subject>Kinases</subject><subject>Medical sciences</subject><subject>Metabolic syndrome</subject><subject>Metabolism</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Isoforms</subject><subject>Proteins</subject><subject>Psycholeptics: tranquillizer, neuroleptic</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Psychoses</subject><subject>Psychotropic drugs</subject><subject>Rodents</subject><subject>Schizophrenia</subject><subject>Schizophrenia - drug therapy</subject><subject>Schizophrenia - genetics</subject><subject>Signal Transduction - drug effects</subject><subject>Wnt Proteins - genetics</subject><issn>0002-953X</issn><issn>1535-7228</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1v0zAUhi3ExMrgL0wWEuIqnT_i2L5BqgZsiEmbKAjujOs4jUtqZ7YDKr9-6dqVjxuuLMvPOec9fgA4xWiKMa_OdN-7qV71U4KQnCKBCRacPgITzCgrOCHiMZgghEghGf16DJ6mtBqviHLyBBxjKTFnkk7At4-hswmGBubWwtn3fHYx_1BQqH0Nv_gM527pdef8Et7o3P7UmwSdh3PTul-hb6P1Tt-zM59dnzamDdkZ-CYOSzgz2QX_DBw1ukv2-f48AZ_fvf10fllcXV-8P59dFZoJlItKlsYwLglleGGE4ZbVtiK4obauKW8EH9emtVhU3FJDy8ry0mihkUV1gy2nJ-D1rm8_LNa2NtbnqDvVR7fWcaOCdurvF-9atQw_FCUlE1U1Nni1bxDD7WBTVmuXjO067W0YkuKUirISuBzJF_-QqzDE8ZuSIgThspRCjlC1g0wMKUXbHKJgpLYK1VahGhWqrUL1oHAsPP1zkd9le2cj8HIP6GR010TtjUsHjhDOSIm2CeiOux90iPif8XdbWrc2</recordid><startdate>20100401</startdate><enddate>20100401</enddate><creator>Freyberg, Zachary</creator><creator>Ferrando, Stephen J</creator><creator>Javitch, Jonathan A</creator><general>American Psychiatric Association</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100401</creationdate><title>Roles of the Akt/GSK-3 and Wnt Signaling Pathways in Schizophrenia and Antipsychotic Drug Action</title><author>Freyberg, Zachary ; Ferrando, Stephen J ; Javitch, Jonathan A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a580t-694cc5792351bc8c7e5de621f3edd37f871173d8b67e3c346e74ca8a0e0df1e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Adaptor Proteins, Signal Transducing - physiology</topic><topic>Adult and adolescent clinical studies</topic><topic>Antipsychotic Agents - pharmacology</topic><topic>Antipsychotic Agents - therapeutic use</topic><topic>Apoptosis</topic><topic>Apoptosis Regulatory Proteins - genetics</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Apoptosis Regulatory Proteins - physiology</topic><topic>Arrestins - antagonists & inhibitors</topic><topic>beta Catenin - antagonists & inhibitors</topic><topic>Biological and medical sciences</topic><topic>Drugs</topic><topic>Glycogen Synthase Kinase 3 - genetics</topic><topic>Glycogen Synthase Kinase 3 - metabolism</topic><topic>Glycogen Synthase Kinase 3 - physiology</topic><topic>Humans</topic><topic>Kinases</topic><topic>Medical sciences</topic><topic>Metabolic syndrome</topic><topic>Metabolism</topic><topic>Neuropharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Isoforms</topic><topic>Proteins</topic><topic>Psycholeptics: tranquillizer, neuroleptic</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Psychoses</topic><topic>Psychotropic drugs</topic><topic>Rodents</topic><topic>Schizophrenia</topic><topic>Schizophrenia - drug therapy</topic><topic>Schizophrenia - genetics</topic><topic>Signal Transduction - drug effects</topic><topic>Wnt Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Freyberg, Zachary</creatorcontrib><creatorcontrib>Ferrando, Stephen J</creatorcontrib><creatorcontrib>Javitch, Jonathan A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American Journal of Psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Freyberg, Zachary</au><au>Ferrando, Stephen J</au><au>Javitch, Jonathan A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Roles of the Akt/GSK-3 and Wnt Signaling Pathways in Schizophrenia and Antipsychotic Drug Action</atitle><jtitle>American Journal of Psychiatry</jtitle><addtitle>Am J Psychiatry</addtitle><date>2010-04-01</date><risdate>2010</risdate><volume>167</volume><issue>4</issue><spage>388</spage><epage>396</epage><pages>388-396</pages><issn>0002-953X</issn><eissn>1535-7228</eissn><coden>AJPSAO</coden><abstract>AbstractDopamine D2 receptor antagonism is a unifying property of all antipsychotic drugs in clinical use. Remarkably, the effector molecules through which these medications exert their actions remain poorly characterized. Increasing attention is being focused on Akt/glycogen synthase kinase-3 (GSK-3) and wingless (Wnt) signaling pathways, which have been associated with schizophrenia in a number of genetic and postmortem studies. Antipsychotic medications may treat symptoms of psychosis, at least in part, through modulation of levels and activity of Akt, GSK-3, and Wnt-related intracellular signaling. The authors review evidence that Akt/GSK-3 and Wnt-related pathways are involved in the pathogenesis of schizophrenia as well as details of intracellular events related to these molecules mediated by both typical and atypical antipsychotic medications. 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| source | MEDLINE; American Psychiatric Publishing Journals (1997-Present); Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Adaptor Proteins, Signal Transducing - physiology Adult and adolescent clinical studies Antipsychotic Agents - pharmacology Antipsychotic Agents - therapeutic use Apoptosis Apoptosis Regulatory Proteins - genetics Apoptosis Regulatory Proteins - metabolism Apoptosis Regulatory Proteins - physiology Arrestins - antagonists & inhibitors beta Catenin - antagonists & inhibitors Biological and medical sciences Drugs Glycogen Synthase Kinase 3 - genetics Glycogen Synthase Kinase 3 - metabolism Glycogen Synthase Kinase 3 - physiology Humans Kinases Medical sciences Metabolic syndrome Metabolism Neuropharmacology Pharmacology. Drug treatments Protein Isoforms Proteins Psycholeptics: tranquillizer, neuroleptic Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychopharmacology Psychoses Psychotropic drugs Rodents Schizophrenia Schizophrenia - drug therapy Schizophrenia - genetics Signal Transduction - drug effects Wnt Proteins - genetics |
| title | Roles of the Akt/GSK-3 and Wnt Signaling Pathways in Schizophrenia and Antipsychotic Drug Action |
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