Inflammatory Stress on Autophagy in Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease during 24 Months of Follow-Up
Recent findings indicate that microglia in Alzheimer's disease (AD) is senescent whereas peripheral blood mononuclear cells (PBMCs) could infiltrate the brain to phagocyte amyloid deposits. However, the molecular mechanisms involved in the amyloid peptide clearance remain unknown. Autophagy is...
Gespeichert in:
| Veröffentlicht in: | PloS one 2015-09, Vol.10 (9), p.e0138326-e0138326 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0138326 |
|---|---|
| container_issue | 9 |
| container_start_page | e0138326 |
| container_title | PloS one |
| container_volume | 10 |
| creator | François, Arnaud Julian, Adrien Ragot, Stéphanie Dugast, Emilie Blanchard, Ludovic Brishoual, Sonia Terro, Faraj Chassaing, Damien Page, Guylène Paccalin, Marc |
| description | Recent findings indicate that microglia in Alzheimer's disease (AD) is senescent whereas peripheral blood mononuclear cells (PBMCs) could infiltrate the brain to phagocyte amyloid deposits. However, the molecular mechanisms involved in the amyloid peptide clearance remain unknown. Autophagy is a physiological degradation of proteins and organelles and can be controlled by pro-inflammatory cytokines. The purpose of this study was to evaluate the impact of inflammation on autophagy in PBMCs from AD patients at baseline, 12 and 24 months of follow-up. Furthermore, PBMCs from healthy patients were also included and treated with 20 μM amyloid peptide 1-42 to mimic AD environment. For each patient, PBMCs were stimulated with the mitogenic factor, phytohaemagglutin (PHA), and treated with either 1 μM C16 as an anti-inflammatory drug or its vehicle. Autophagic markers (Beclin-1, p62/sequestosome 1 and microtubule-associated protein-light chain 3: LC3) were quantified by western blot and cytokines (Interleukin (IL)-1β, Tumor necrosis Factor (TNF)-α and IL-6) by Luminex X-MAP® technology. Beclin-1 and TNF-α levels were inversely correlated in AD PBMCs at 12 months post-inclusion. In addition, Beclin-1 and p62 increased in the low inflammatory environment induced by C16. Only LC3-I levels were inversely correlated with cognitive decline at baseline. For the first time, this study describes longitudinal changes in autophagic markers in PBMCs of AD patients under an inflammatory environment. Inflammation would induce autophagy in the PBMCs of AD patients while an anti-inflammatory environment could inhibit their autophagic response. However, this positive response could be altered in a highly aggressive environment. |
| doi_str_mv | 10.1371/journal.pone.0138326 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1719292390</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A471193637</galeid><doaj_id>oai_doaj_org_article_0c28d3117ccd46208dd1d6efe152c111</doaj_id><sourcerecordid>A471193637</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-4a0c4ce8a9be06c36a4635b2d05cb75008b809736f672e9e4fd591505ef1fe933</originalsourceid><addsrcrecordid>eNqNk11v0zAUhiMEYmPwDxBYQuLjosUfiZPcIJXCoNLQJsa4tVznpPHk2MV2GOUv8Kdx125q0S6QL2zZz3mP_fqcLHtK8Jiwkry9dIO30oyXzsIYE1Yxyu9lh6RmdMQpZvd31gfZoxAuMS5YxfnD7IByVrMKk8Psz8y2Rva9jM6v0Hn0EAJyFk2G6JadXKyQtugMvF524KVB741zDfrirLODMiA9moIxAbXe9ehMRg02BnSlY4cm5ncHugf_KqAPOoAMgJrBa7tANF9LxC6latGxM8ZdjS6Wj7MHrTQBnmzno-zi-OO36efRyemn2XRyMlK8pnGUS6xyBZWs54C5YlzmnBVz2uBCzcsC42pe4bpkvOUlhRrytilqUuACWtJCzdhR9nyjuzQuiK2PQZCS1LSmrMaJmG2IxslLsfS6l34lnNTiesP5hZA-6mSAwIpWDSOkVKrJk9dV05CGQwukoIoQkrTebbMN8x4alQxKRu6J7p9Y3YmF-ynyoqzqYn3d11sB734MEKLodVDJdWnBDdf3LvOSMlYk9MU_6N2v21ILmR6gbetSXrUWFZO8JKlqOCsTNb6DSqOBXqtUdK1O-3sBb_YCEhPhV1zIIQQxO__6_-zp93325Q7bgTSpcJwZonY27IP5BlTeheChvTWZYLHumRs3xLpnxLZnUtiz3Q-6DbppEvYXGugR6w</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1719292390</pqid></control><display><type>article</type><title>Inflammatory Stress on Autophagy in Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease during 24 Months of Follow-Up</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>François, Arnaud ; Julian, Adrien ; Ragot, Stéphanie ; Dugast, Emilie ; Blanchard, Ludovic ; Brishoual, Sonia ; Terro, Faraj ; Chassaing, Damien ; Page, Guylène ; Paccalin, Marc</creator><creatorcontrib>François, Arnaud ; Julian, Adrien ; Ragot, Stéphanie ; Dugast, Emilie ; Blanchard, Ludovic ; Brishoual, Sonia ; Terro, Faraj ; Chassaing, Damien ; Page, Guylène ; Paccalin, Marc</creatorcontrib><description>Recent findings indicate that microglia in Alzheimer's disease (AD) is senescent whereas peripheral blood mononuclear cells (PBMCs) could infiltrate the brain to phagocyte amyloid deposits. However, the molecular mechanisms involved in the amyloid peptide clearance remain unknown. Autophagy is a physiological degradation of proteins and organelles and can be controlled by pro-inflammatory cytokines. The purpose of this study was to evaluate the impact of inflammation on autophagy in PBMCs from AD patients at baseline, 12 and 24 months of follow-up. Furthermore, PBMCs from healthy patients were also included and treated with 20 μM amyloid peptide 1-42 to mimic AD environment. For each patient, PBMCs were stimulated with the mitogenic factor, phytohaemagglutin (PHA), and treated with either 1 μM C16 as an anti-inflammatory drug or its vehicle. Autophagic markers (Beclin-1, p62/sequestosome 1 and microtubule-associated protein-light chain 3: LC3) were quantified by western blot and cytokines (Interleukin (IL)-1β, Tumor necrosis Factor (TNF)-α and IL-6) by Luminex X-MAP® technology. Beclin-1 and TNF-α levels were inversely correlated in AD PBMCs at 12 months post-inclusion. In addition, Beclin-1 and p62 increased in the low inflammatory environment induced by C16. Only LC3-I levels were inversely correlated with cognitive decline at baseline. For the first time, this study describes longitudinal changes in autophagic markers in PBMCs of AD patients under an inflammatory environment. Inflammation would induce autophagy in the PBMCs of AD patients while an anti-inflammatory environment could inhibit their autophagic response. However, this positive response could be altered in a highly aggressive environment.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0138326</identifier><identifier>PMID: 26393801</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Advertising executives ; Aged ; Aged, 80 and over ; Alzheimer Disease - blood ; Alzheimer's disease ; Amyotrophic lateral sclerosis ; Anti-inflammatory agents ; Apoptosis ; Autophagy ; Biodegradation ; Blood ; Bone marrow ; Brain ; Brain research ; Cell death ; Cognitive ability ; Cytokines ; Environments ; Female ; Follow-Up Studies ; Geriatrics ; Homeostasis ; Humans ; Inflammation ; Interleukin 6 ; Leukocytes (mononuclear) ; Life assessment ; Lymphocytes ; Male ; Markers ; Medical research ; Microglia ; Middle Aged ; Mitogenic factor ; Molecular modelling ; Monocytes - immunology ; Neurodegenerative diseases ; Organelles ; Pathology ; Patients ; Peripheral blood mononuclear cells ; Phagocytosis ; Proteins ; Proteolysis ; Rodents ; Tumor necrosis factor-α ; β-Amyloid</subject><ispartof>PloS one, 2015-09, Vol.10 (9), p.e0138326-e0138326</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 François et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 François et al 2015 François et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-4a0c4ce8a9be06c36a4635b2d05cb75008b809736f672e9e4fd591505ef1fe933</citedby><cites>FETCH-LOGICAL-c692t-4a0c4ce8a9be06c36a4635b2d05cb75008b809736f672e9e4fd591505ef1fe933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578953/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578953/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26393801$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>François, Arnaud</creatorcontrib><creatorcontrib>Julian, Adrien</creatorcontrib><creatorcontrib>Ragot, Stéphanie</creatorcontrib><creatorcontrib>Dugast, Emilie</creatorcontrib><creatorcontrib>Blanchard, Ludovic</creatorcontrib><creatorcontrib>Brishoual, Sonia</creatorcontrib><creatorcontrib>Terro, Faraj</creatorcontrib><creatorcontrib>Chassaing, Damien</creatorcontrib><creatorcontrib>Page, Guylène</creatorcontrib><creatorcontrib>Paccalin, Marc</creatorcontrib><title>Inflammatory Stress on Autophagy in Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease during 24 Months of Follow-Up</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Recent findings indicate that microglia in Alzheimer's disease (AD) is senescent whereas peripheral blood mononuclear cells (PBMCs) could infiltrate the brain to phagocyte amyloid deposits. However, the molecular mechanisms involved in the amyloid peptide clearance remain unknown. Autophagy is a physiological degradation of proteins and organelles and can be controlled by pro-inflammatory cytokines. The purpose of this study was to evaluate the impact of inflammation on autophagy in PBMCs from AD patients at baseline, 12 and 24 months of follow-up. Furthermore, PBMCs from healthy patients were also included and treated with 20 μM amyloid peptide 1-42 to mimic AD environment. For each patient, PBMCs were stimulated with the mitogenic factor, phytohaemagglutin (PHA), and treated with either 1 μM C16 as an anti-inflammatory drug or its vehicle. Autophagic markers (Beclin-1, p62/sequestosome 1 and microtubule-associated protein-light chain 3: LC3) were quantified by western blot and cytokines (Interleukin (IL)-1β, Tumor necrosis Factor (TNF)-α and IL-6) by Luminex X-MAP® technology. Beclin-1 and TNF-α levels were inversely correlated in AD PBMCs at 12 months post-inclusion. In addition, Beclin-1 and p62 increased in the low inflammatory environment induced by C16. Only LC3-I levels were inversely correlated with cognitive decline at baseline. For the first time, this study describes longitudinal changes in autophagic markers in PBMCs of AD patients under an inflammatory environment. Inflammation would induce autophagy in the PBMCs of AD patients while an anti-inflammatory environment could inhibit their autophagic response. However, this positive response could be altered in a highly aggressive environment.</description><subject>Adult</subject><subject>Advertising executives</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - blood</subject><subject>Alzheimer's disease</subject><subject>Amyotrophic lateral sclerosis</subject><subject>Anti-inflammatory agents</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Biodegradation</subject><subject>Blood</subject><subject>Bone marrow</subject><subject>Brain</subject><subject>Brain research</subject><subject>Cell death</subject><subject>Cognitive ability</subject><subject>Cytokines</subject><subject>Environments</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Geriatrics</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Leukocytes (mononuclear)</subject><subject>Life assessment</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Markers</subject><subject>Medical research</subject><subject>Microglia</subject><subject>Middle Aged</subject><subject>Mitogenic factor</subject><subject>Molecular modelling</subject><subject>Monocytes - immunology</subject><subject>Neurodegenerative diseases</subject><subject>Organelles</subject><subject>Pathology</subject><subject>Patients</subject><subject>Peripheral blood mononuclear cells</subject><subject>Phagocytosis</subject><subject>Proteins</subject><subject>Proteolysis</subject><subject>Rodents</subject><subject>Tumor necrosis factor-α</subject><subject>β-Amyloid</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYmPwDxBYQuLjosUfiZPcIJXCoNLQJsa4tVznpPHk2MV2GOUv8Kdx125q0S6QL2zZz3mP_fqcLHtK8Jiwkry9dIO30oyXzsIYE1Yxyu9lh6RmdMQpZvd31gfZoxAuMS5YxfnD7IByVrMKk8Psz8y2Rva9jM6v0Hn0EAJyFk2G6JadXKyQtugMvF524KVB741zDfrirLODMiA9moIxAbXe9ehMRg02BnSlY4cm5ncHugf_KqAPOoAMgJrBa7tANF9LxC6latGxM8ZdjS6Wj7MHrTQBnmzno-zi-OO36efRyemn2XRyMlK8pnGUS6xyBZWs54C5YlzmnBVz2uBCzcsC42pe4bpkvOUlhRrytilqUuACWtJCzdhR9nyjuzQuiK2PQZCS1LSmrMaJmG2IxslLsfS6l34lnNTiesP5hZA-6mSAwIpWDSOkVKrJk9dV05CGQwukoIoQkrTebbMN8x4alQxKRu6J7p9Y3YmF-ynyoqzqYn3d11sB734MEKLodVDJdWnBDdf3LvOSMlYk9MU_6N2v21ILmR6gbetSXrUWFZO8JKlqOCsTNb6DSqOBXqtUdK1O-3sBb_YCEhPhV1zIIQQxO__6_-zp93325Q7bgTSpcJwZonY27IP5BlTeheChvTWZYLHumRs3xLpnxLZnUtiz3Q-6DbppEvYXGugR6w</recordid><startdate>20150922</startdate><enddate>20150922</enddate><creator>François, Arnaud</creator><creator>Julian, Adrien</creator><creator>Ragot, Stéphanie</creator><creator>Dugast, Emilie</creator><creator>Blanchard, Ludovic</creator><creator>Brishoual, Sonia</creator><creator>Terro, Faraj</creator><creator>Chassaing, Damien</creator><creator>Page, Guylène</creator><creator>Paccalin, Marc</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150922</creationdate><title>Inflammatory Stress on Autophagy in Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease during 24 Months of Follow-Up</title><author>François, Arnaud ; Julian, Adrien ; Ragot, Stéphanie ; Dugast, Emilie ; Blanchard, Ludovic ; Brishoual, Sonia ; Terro, Faraj ; Chassaing, Damien ; Page, Guylène ; Paccalin, Marc</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-4a0c4ce8a9be06c36a4635b2d05cb75008b809736f672e9e4fd591505ef1fe933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Advertising executives</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alzheimer Disease - blood</topic><topic>Alzheimer's disease</topic><topic>Amyotrophic lateral sclerosis</topic><topic>Anti-inflammatory agents</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Biodegradation</topic><topic>Blood</topic><topic>Bone marrow</topic><topic>Brain</topic><topic>Brain research</topic><topic>Cell death</topic><topic>Cognitive ability</topic><topic>Cytokines</topic><topic>Environments</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Geriatrics</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Leukocytes (mononuclear)</topic><topic>Life assessment</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Markers</topic><topic>Medical research</topic><topic>Microglia</topic><topic>Middle Aged</topic><topic>Mitogenic factor</topic><topic>Molecular modelling</topic><topic>Monocytes - immunology</topic><topic>Neurodegenerative diseases</topic><topic>Organelles</topic><topic>Pathology</topic><topic>Patients</topic><topic>Peripheral blood mononuclear cells</topic><topic>Phagocytosis</topic><topic>Proteins</topic><topic>Proteolysis</topic><topic>Rodents</topic><topic>Tumor necrosis factor-α</topic><topic>β-Amyloid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>François, Arnaud</creatorcontrib><creatorcontrib>Julian, Adrien</creatorcontrib><creatorcontrib>Ragot, Stéphanie</creatorcontrib><creatorcontrib>Dugast, Emilie</creatorcontrib><creatorcontrib>Blanchard, Ludovic</creatorcontrib><creatorcontrib>Brishoual, Sonia</creatorcontrib><creatorcontrib>Terro, Faraj</creatorcontrib><creatorcontrib>Chassaing, Damien</creatorcontrib><creatorcontrib>Page, Guylène</creatorcontrib><creatorcontrib>Paccalin, Marc</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>François, Arnaud</au><au>Julian, Adrien</au><au>Ragot, Stéphanie</au><au>Dugast, Emilie</au><au>Blanchard, Ludovic</au><au>Brishoual, Sonia</au><au>Terro, Faraj</au><au>Chassaing, Damien</au><au>Page, Guylène</au><au>Paccalin, Marc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inflammatory Stress on Autophagy in Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease during 24 Months of Follow-Up</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-09-22</date><risdate>2015</risdate><volume>10</volume><issue>9</issue><spage>e0138326</spage><epage>e0138326</epage><pages>e0138326-e0138326</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Recent findings indicate that microglia in Alzheimer's disease (AD) is senescent whereas peripheral blood mononuclear cells (PBMCs) could infiltrate the brain to phagocyte amyloid deposits. However, the molecular mechanisms involved in the amyloid peptide clearance remain unknown. Autophagy is a physiological degradation of proteins and organelles and can be controlled by pro-inflammatory cytokines. The purpose of this study was to evaluate the impact of inflammation on autophagy in PBMCs from AD patients at baseline, 12 and 24 months of follow-up. Furthermore, PBMCs from healthy patients were also included and treated with 20 μM amyloid peptide 1-42 to mimic AD environment. For each patient, PBMCs were stimulated with the mitogenic factor, phytohaemagglutin (PHA), and treated with either 1 μM C16 as an anti-inflammatory drug or its vehicle. Autophagic markers (Beclin-1, p62/sequestosome 1 and microtubule-associated protein-light chain 3: LC3) were quantified by western blot and cytokines (Interleukin (IL)-1β, Tumor necrosis Factor (TNF)-α and IL-6) by Luminex X-MAP® technology. Beclin-1 and TNF-α levels were inversely correlated in AD PBMCs at 12 months post-inclusion. In addition, Beclin-1 and p62 increased in the low inflammatory environment induced by C16. Only LC3-I levels were inversely correlated with cognitive decline at baseline. For the first time, this study describes longitudinal changes in autophagic markers in PBMCs of AD patients under an inflammatory environment. Inflammation would induce autophagy in the PBMCs of AD patients while an anti-inflammatory environment could inhibit their autophagic response. However, this positive response could be altered in a highly aggressive environment.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26393801</pmid><doi>10.1371/journal.pone.0138326</doi><tpages>e0138326</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-09, Vol.10 (9), p.e0138326-e0138326 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1719292390 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Advertising executives Aged Aged, 80 and over Alzheimer Disease - blood Alzheimer's disease Amyotrophic lateral sclerosis Anti-inflammatory agents Apoptosis Autophagy Biodegradation Blood Bone marrow Brain Brain research Cell death Cognitive ability Cytokines Environments Female Follow-Up Studies Geriatrics Homeostasis Humans Inflammation Interleukin 6 Leukocytes (mononuclear) Life assessment Lymphocytes Male Markers Medical research Microglia Middle Aged Mitogenic factor Molecular modelling Monocytes - immunology Neurodegenerative diseases Organelles Pathology Patients Peripheral blood mononuclear cells Phagocytosis Proteins Proteolysis Rodents Tumor necrosis factor-α β-Amyloid |
| title | Inflammatory Stress on Autophagy in Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease during 24 Months of Follow-Up |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T06%3A56%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inflammatory%20Stress%20on%20Autophagy%20in%20Peripheral%20Blood%20Mononuclear%20Cells%20from%20Patients%20with%20Alzheimer's%20Disease%20during%2024%20Months%20of%20Follow-Up&rft.jtitle=PloS%20one&rft.au=Fran%C3%A7ois,%20Arnaud&rft.date=2015-09-22&rft.volume=10&rft.issue=9&rft.spage=e0138326&rft.epage=e0138326&rft.pages=e0138326-e0138326&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0138326&rft_dat=%3Cgale_plos_%3EA471193637%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1719292390&rft_id=info:pmid/26393801&rft_galeid=A471193637&rft_doaj_id=oai_doaj_org_article_0c28d3117ccd46208dd1d6efe152c111&rfr_iscdi=true |