Interleukin-1 promotion of MAPK-p38 overexpression in experimental animals and in Alzheimer's disease: potential significance for tau protein phosphorylation
Activated (phosphorylated) mitogen-activated protein kinase p38 (MAPK-p38) and interleukin-1 (IL-1) have both been implicated in the hyperphosphorylation of tau, a major component of the neurofibrillary tangles in Alzheimer's disease. This, together with findings showing that IL-1 activates MAP...
Gespeichert in:
| Veröffentlicht in: | Neurochemistry international 2001-11, Vol.39 (5), p.341-348 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 348 |
|---|---|
| container_issue | 5 |
| container_start_page | 341 |
| container_title | Neurochemistry international |
| container_volume | 39 |
| creator | Sheng, Jin G. Jones, Richard A. Zhou, Xue Q. McGinness, John M. Van Eldik, Linda J. Mrak, Robert E. Griffin, W.Sue T. |
| description | Activated (phosphorylated) mitogen-activated protein kinase p38 (MAPK-p38) and interleukin-1 (IL-1) have both been implicated in the hyperphosphorylation of tau, a major component of the neurofibrillary tangles in Alzheimer's disease. This, together with findings showing that IL-1 activates MAPK-p38 in vitro and is markedly overexpressed in Alzheimer brain, suggest a role for IL-1-induced MAPK-p38 activation in the genesis of neurofibrillary pathology in Alzheimer's disease. We found frequent colocalization of hyperphosphorylated tau protein (AT8 antibody) and activated MAPK-p38 in neurons and in dystrophic neurites in Alzheimer brain, and frequent association of these structures with activated microglia overexpressing IL-1. Tissue levels of IL-1 mRNA as well as of both phosphorylated and non-phosphorylated isoforms of tau were elevated in these brains. Significant correlations were found between the numbers of AT8- and MAPK-p38-immunoreactive neurons, and between the numbers of activated microglia overexpressing IL-1 and the numbers of both AT8- and MAPK-p38-immunoreactive neurons. Furthermore, rats bearing IL-1-impregnated pellets showed a six- to seven-fold increase in the levels of MAPK-p38 mRNA, compared with rats with vehicle-only pellets (
P |
| doi_str_mv | 10.1016/S0197-0186(01)00041-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3833633</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0197018601000419</els_id><sourcerecordid>71230306</sourcerecordid><originalsourceid>FETCH-LOGICAL-c546t-f76fa1328c9060178cb9a7393c7f2da473147291330827c383185e8f64b606fb3</originalsourceid><addsrcrecordid>eNqFkktv1DAQxy0EokvhI4B84nEI2HHiRw-gVcWjoggk4Gx5nXHXkNjBTlaU78J3xemuCpx6sEfW_OY_M55B6CElzymh_MVnQpWoCJX8KaHPCCENrdQttKJS1JUSbXMbra6RI3Qv528FEoq0d9ERpa2QgqsV-n0WJkg9zN99qCgeUxzi5GPA0eEP60_vq5FJHHeQ4OeYIOfF5QMuL0h-gDCZHpvgB9PnYrvFt-5_baH40pOMO5_BZDjBY5wK7Aud_UXwzlsTLGAXE57MvOSdoMSO25jLSZe9Waq4j-64ogwPDvYYfX3z-svpu-r849uz0_V5ZduGT5UT3BnKamkV4YQKaTfKCKaYFa7uTCMYbUStKGNE1sIyyahsQTrebDjhbsOO0cu97jhvBuhsKTWZXo-lRZMudTRe_-8Jfqsv4k4XKcYZKwKPDwIp_pghT3rw2ULfmwBxzlrQmhFG-I0glawlNW8K2O5Bm2LOCdx1NZToZQP01QboZbzl0lcboFWJe_RvK3-jDiMvwKs9AOVDdx6SztZDGUbnE9hJd9HfkOIPpsPD5g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>18350264</pqid></control><display><type>article</type><title>Interleukin-1 promotion of MAPK-p38 overexpression in experimental animals and in Alzheimer's disease: potential significance for tau protein phosphorylation</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Sheng, Jin G. ; Jones, Richard A. ; Zhou, Xue Q. ; McGinness, John M. ; Van Eldik, Linda J. ; Mrak, Robert E. ; Griffin, W.Sue T.</creator><creatorcontrib>Sheng, Jin G. ; Jones, Richard A. ; Zhou, Xue Q. ; McGinness, John M. ; Van Eldik, Linda J. ; Mrak, Robert E. ; Griffin, W.Sue T.</creatorcontrib><description>Activated (phosphorylated) mitogen-activated protein kinase p38 (MAPK-p38) and interleukin-1 (IL-1) have both been implicated in the hyperphosphorylation of tau, a major component of the neurofibrillary tangles in Alzheimer's disease. This, together with findings showing that IL-1 activates MAPK-p38 in vitro and is markedly overexpressed in Alzheimer brain, suggest a role for IL-1-induced MAPK-p38 activation in the genesis of neurofibrillary pathology in Alzheimer's disease. We found frequent colocalization of hyperphosphorylated tau protein (AT8 antibody) and activated MAPK-p38 in neurons and in dystrophic neurites in Alzheimer brain, and frequent association of these structures with activated microglia overexpressing IL-1. Tissue levels of IL-1 mRNA as well as of both phosphorylated and non-phosphorylated isoforms of tau were elevated in these brains. Significant correlations were found between the numbers of AT8- and MAPK-p38-immunoreactive neurons, and between the numbers of activated microglia overexpressing IL-1 and the numbers of both AT8- and MAPK-p38-immunoreactive neurons. Furthermore, rats bearing IL-1-impregnated pellets showed a six- to seven-fold increase in the levels of MAPK-p38 mRNA, compared with rats with vehicle-only pellets (
P<0.0001). These results suggest that microglial activation and IL-1 overexpression are part of a feedback cascade in which MAPK-p38 overexpression and activation leads to tau hyperphosphorylation and neurofibrillary pathology in Alzheimer's disease.</description><identifier>ISSN: 0197-0186</identifier><identifier>EISSN: 1872-9754</identifier><identifier>DOI: 10.1016/S0197-0186(01)00041-9</identifier><identifier>PMID: 11578769</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Aged ; Aged, 80 and over ; Alzheimer Disease - metabolism ; Alzheimer's disease ; Animals ; AT8 ; Blotting, Western ; Brain - enzymology ; Female ; Humans ; Interleukin-1 ; Interleukin-1 - genetics ; Interleukin-1 - metabolism ; Interleukin-1 - pharmacology ; Interleukin-1 - physiology ; Male ; MAPK-p38 ; Middle Aged ; Mitogen-Activated Protein Kinases - metabolism ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Tau phosphorylation ; tau Proteins - metabolism</subject><ispartof>Neurochemistry international, 2001-11, Vol.39 (5), p.341-348</ispartof><rights>2001</rights><rights>2001 Published by Elsevier Science Ltd. 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c546t-f76fa1328c9060178cb9a7393c7f2da473147291330827c383185e8f64b606fb3</citedby><cites>FETCH-LOGICAL-c546t-f76fa1328c9060178cb9a7393c7f2da473147291330827c383185e8f64b606fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0197-0186(01)00041-9$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,778,782,883,3539,27911,27912,45982</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11578769$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sheng, Jin G.</creatorcontrib><creatorcontrib>Jones, Richard A.</creatorcontrib><creatorcontrib>Zhou, Xue Q.</creatorcontrib><creatorcontrib>McGinness, John M.</creatorcontrib><creatorcontrib>Van Eldik, Linda J.</creatorcontrib><creatorcontrib>Mrak, Robert E.</creatorcontrib><creatorcontrib>Griffin, W.Sue T.</creatorcontrib><title>Interleukin-1 promotion of MAPK-p38 overexpression in experimental animals and in Alzheimer's disease: potential significance for tau protein phosphorylation</title><title>Neurochemistry international</title><addtitle>Neurochem Int</addtitle><description>Activated (phosphorylated) mitogen-activated protein kinase p38 (MAPK-p38) and interleukin-1 (IL-1) have both been implicated in the hyperphosphorylation of tau, a major component of the neurofibrillary tangles in Alzheimer's disease. This, together with findings showing that IL-1 activates MAPK-p38 in vitro and is markedly overexpressed in Alzheimer brain, suggest a role for IL-1-induced MAPK-p38 activation in the genesis of neurofibrillary pathology in Alzheimer's disease. We found frequent colocalization of hyperphosphorylated tau protein (AT8 antibody) and activated MAPK-p38 in neurons and in dystrophic neurites in Alzheimer brain, and frequent association of these structures with activated microglia overexpressing IL-1. Tissue levels of IL-1 mRNA as well as of both phosphorylated and non-phosphorylated isoforms of tau were elevated in these brains. Significant correlations were found between the numbers of AT8- and MAPK-p38-immunoreactive neurons, and between the numbers of activated microglia overexpressing IL-1 and the numbers of both AT8- and MAPK-p38-immunoreactive neurons. Furthermore, rats bearing IL-1-impregnated pellets showed a six- to seven-fold increase in the levels of MAPK-p38 mRNA, compared with rats with vehicle-only pellets (
P<0.0001). These results suggest that microglial activation and IL-1 overexpression are part of a feedback cascade in which MAPK-p38 overexpression and activation leads to tau hyperphosphorylation and neurofibrillary pathology in Alzheimer's disease.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>AT8</subject><subject>Blotting, Western</subject><subject>Brain - enzymology</subject><subject>Female</subject><subject>Humans</subject><subject>Interleukin-1</subject><subject>Interleukin-1 - genetics</subject><subject>Interleukin-1 - metabolism</subject><subject>Interleukin-1 - pharmacology</subject><subject>Interleukin-1 - physiology</subject><subject>Male</subject><subject>MAPK-p38</subject><subject>Middle Aged</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>p38 Mitogen-Activated Protein Kinases</subject><subject>Phosphorylation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Tau phosphorylation</subject><subject>tau Proteins - metabolism</subject><issn>0197-0186</issn><issn>1872-9754</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktv1DAQxy0EokvhI4B84nEI2HHiRw-gVcWjoggk4Gx5nXHXkNjBTlaU78J3xemuCpx6sEfW_OY_M55B6CElzymh_MVnQpWoCJX8KaHPCCENrdQttKJS1JUSbXMbra6RI3Qv528FEoq0d9ERpa2QgqsV-n0WJkg9zN99qCgeUxzi5GPA0eEP60_vq5FJHHeQ4OeYIOfF5QMuL0h-gDCZHpvgB9PnYrvFt-5_baH40pOMO5_BZDjBY5wK7Aud_UXwzlsTLGAXE57MvOSdoMSO25jLSZe9Waq4j-64ogwPDvYYfX3z-svpu-r849uz0_V5ZduGT5UT3BnKamkV4YQKaTfKCKaYFa7uTCMYbUStKGNE1sIyyahsQTrebDjhbsOO0cu97jhvBuhsKTWZXo-lRZMudTRe_-8Jfqsv4k4XKcYZKwKPDwIp_pghT3rw2ULfmwBxzlrQmhFG-I0glawlNW8K2O5Bm2LOCdx1NZToZQP01QboZbzl0lcboFWJe_RvK3-jDiMvwKs9AOVDdx6SztZDGUbnE9hJd9HfkOIPpsPD5g</recordid><startdate>20011101</startdate><enddate>20011101</enddate><creator>Sheng, Jin G.</creator><creator>Jones, Richard A.</creator><creator>Zhou, Xue Q.</creator><creator>McGinness, John M.</creator><creator>Van Eldik, Linda J.</creator><creator>Mrak, Robert E.</creator><creator>Griffin, W.Sue T.</creator><general>Elsevier Ltd</general><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>7TK</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20011101</creationdate><title>Interleukin-1 promotion of MAPK-p38 overexpression in experimental animals and in Alzheimer's disease: potential significance for tau protein phosphorylation</title><author>Sheng, Jin G. ; Jones, Richard A. ; Zhou, Xue Q. ; McGinness, John M. ; Van Eldik, Linda J. ; Mrak, Robert E. ; Griffin, W.Sue T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c546t-f76fa1328c9060178cb9a7393c7f2da473147291330827c383185e8f64b606fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer's disease</topic><topic>Animals</topic><topic>AT8</topic><topic>Blotting, Western</topic><topic>Brain - enzymology</topic><topic>Female</topic><topic>Humans</topic><topic>Interleukin-1</topic><topic>Interleukin-1 - genetics</topic><topic>Interleukin-1 - metabolism</topic><topic>Interleukin-1 - pharmacology</topic><topic>Interleukin-1 - physiology</topic><topic>Male</topic><topic>MAPK-p38</topic><topic>Middle Aged</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>p38 Mitogen-Activated Protein Kinases</topic><topic>Phosphorylation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Tau phosphorylation</topic><topic>tau Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sheng, Jin G.</creatorcontrib><creatorcontrib>Jones, Richard A.</creatorcontrib><creatorcontrib>Zhou, Xue Q.</creatorcontrib><creatorcontrib>McGinness, John M.</creatorcontrib><creatorcontrib>Van Eldik, Linda J.</creatorcontrib><creatorcontrib>Mrak, Robert E.</creatorcontrib><creatorcontrib>Griffin, W.Sue T.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neurochemistry international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sheng, Jin G.</au><au>Jones, Richard A.</au><au>Zhou, Xue Q.</au><au>McGinness, John M.</au><au>Van Eldik, Linda J.</au><au>Mrak, Robert E.</au><au>Griffin, W.Sue T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-1 promotion of MAPK-p38 overexpression in experimental animals and in Alzheimer's disease: potential significance for tau protein phosphorylation</atitle><jtitle>Neurochemistry international</jtitle><addtitle>Neurochem Int</addtitle><date>2001-11-01</date><risdate>2001</risdate><volume>39</volume><issue>5</issue><spage>341</spage><epage>348</epage><pages>341-348</pages><issn>0197-0186</issn><eissn>1872-9754</eissn><abstract>Activated (phosphorylated) mitogen-activated protein kinase p38 (MAPK-p38) and interleukin-1 (IL-1) have both been implicated in the hyperphosphorylation of tau, a major component of the neurofibrillary tangles in Alzheimer's disease. This, together with findings showing that IL-1 activates MAPK-p38 in vitro and is markedly overexpressed in Alzheimer brain, suggest a role for IL-1-induced MAPK-p38 activation in the genesis of neurofibrillary pathology in Alzheimer's disease. We found frequent colocalization of hyperphosphorylated tau protein (AT8 antibody) and activated MAPK-p38 in neurons and in dystrophic neurites in Alzheimer brain, and frequent association of these structures with activated microglia overexpressing IL-1. Tissue levels of IL-1 mRNA as well as of both phosphorylated and non-phosphorylated isoforms of tau were elevated in these brains. Significant correlations were found between the numbers of AT8- and MAPK-p38-immunoreactive neurons, and between the numbers of activated microglia overexpressing IL-1 and the numbers of both AT8- and MAPK-p38-immunoreactive neurons. Furthermore, rats bearing IL-1-impregnated pellets showed a six- to seven-fold increase in the levels of MAPK-p38 mRNA, compared with rats with vehicle-only pellets (
P<0.0001). These results suggest that microglial activation and IL-1 overexpression are part of a feedback cascade in which MAPK-p38 overexpression and activation leads to tau hyperphosphorylation and neurofibrillary pathology in Alzheimer's disease.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>11578769</pmid><doi>10.1016/S0197-0186(01)00041-9</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0197-0186 |
| ispartof | Neurochemistry international, 2001-11, Vol.39 (5), p.341-348 |
| issn | 0197-0186 1872-9754 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3833633 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Aged Aged, 80 and over Alzheimer Disease - metabolism Alzheimer's disease Animals AT8 Blotting, Western Brain - enzymology Female Humans Interleukin-1 Interleukin-1 - genetics Interleukin-1 - metabolism Interleukin-1 - pharmacology Interleukin-1 - physiology Male MAPK-p38 Middle Aged Mitogen-Activated Protein Kinases - metabolism p38 Mitogen-Activated Protein Kinases Phosphorylation Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Tau phosphorylation tau Proteins - metabolism |
| title | Interleukin-1 promotion of MAPK-p38 overexpression in experimental animals and in Alzheimer's disease: potential significance for tau protein phosphorylation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T22%3A45%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Interleukin-1%20promotion%20of%20MAPK-p38%20overexpression%20in%20experimental%20animals%20and%20in%20Alzheimer's%20disease:%20potential%20significance%20for%20tau%20protein%20phosphorylation&rft.jtitle=Neurochemistry%20international&rft.au=Sheng,%20Jin%20G.&rft.date=2001-11-01&rft.volume=39&rft.issue=5&rft.spage=341&rft.epage=348&rft.pages=341-348&rft.issn=0197-0186&rft.eissn=1872-9754&rft_id=info:doi/10.1016/S0197-0186(01)00041-9&rft_dat=%3Cproquest_pubme%3E71230306%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=18350264&rft_id=info:pmid/11578769&rft_els_id=S0197018601000419&rfr_iscdi=true |