Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis
Objective Evaluating the efficacy of 3,6’‐dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline. Background Amyloid‐β (Aβ) or tau‐focused clinical trials hav...
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| Veröffentlicht in: | Alzheimer's & dementia 2022-11, Vol.18 (11), p.2327-2340 |
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| creator | Lecca, Daniela Jung, Yoo Jin Scerba, Michael T. Hwang, Inho Kim, Yu Kyung Kim, Sun Modrow, Sydney Tweedie, David Hsueh, Shih‐Chang Liu, Dong Luo, Weiming Glotfelty, Elliot Li, Yazhou Wang, Jia‐Yi Luo, Yu Hoffer, Barry J. Kim, Dong Seok McDevitt, Ross A. Greig, Nigel H. |
| description | Objective
Evaluating the efficacy of 3,6’‐dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline.
Background
Amyloid‐β (Aβ) or tau‐focused clinical trials have proved unsuccessful in mitigating AD‐associated cognitive impairment. Identification of new drug targets is needed. Neuroinflammation is a therapeutic target in neurodegenerative disorders, and TNF‐α a pivotal neuroinflammatory driver.
New hypothesis
AD‐associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aβ generation will define the role of neuroinflammation in AD progression.
Major challenges
Difficulty of TNF‐α‐lowering compounds reaching brain, and identification of a therapeutic‐time window to preserve the beneficial role of neuroinflammatory processes.
Linkage to other major theories
Microglia/astroglia are heavily implicated in maintenance of synaptic plasticity/function in healthy brain and are disrupted by Aβ. Mitigation of chronic gliosis can restore synaptic homeostasis/cognitive function. |
| doi_str_mv | 10.1002/alz.12610 |
| format | Article |
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Evaluating the efficacy of 3,6’‐dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline.
Background
Amyloid‐β (Aβ) or tau‐focused clinical trials have proved unsuccessful in mitigating AD‐associated cognitive impairment. Identification of new drug targets is needed. Neuroinflammation is a therapeutic target in neurodegenerative disorders, and TNF‐α a pivotal neuroinflammatory driver.
New hypothesis
AD‐associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aβ generation will define the role of neuroinflammation in AD progression.
Major challenges
Difficulty of TNF‐α‐lowering compounds reaching brain, and identification of a therapeutic‐time window to preserve the beneficial role of neuroinflammatory processes.
Linkage to other major theories
Microglia/astroglia are heavily implicated in maintenance of synaptic plasticity/function in healthy brain and are disrupted by Aβ. Mitigation of chronic gliosis can restore synaptic homeostasis/cognitive function.</description><identifier>ISSN: 1552-5260</identifier><identifier>ISSN: 1552-5279</identifier><identifier>EISSN: 1552-5279</identifier><identifier>DOI: 10.1002/alz.12610</identifier><identifier>PMID: 35234334</identifier><language>eng</language><publisher>United States: John Wiley and Sons Inc</publisher><subject>3,6’‐dithioPomalidomide ; 5xFAD mice ; Alzheimer Disease ; Alzheimer pathology ; Amyloid beta-Peptides ; amyloid hypothesis ; Animals ; Cognition ; Cognitive Dysfunction ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microglia ; microglial/astrocyte activation ; neuroinflammation ; Neuroinflammatory Diseases ; Neuronal Plasticity ; TNF‐α ; Tumor Necrosis Factor-alpha</subject><ispartof>Alzheimer's & dementia, 2022-11, Vol.18 (11), p.2327-2340</ispartof><rights>2022 The Authors. published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This article has been contributed to by US Government employees and their work is in the public domain in the USA.</rights><rights>2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This article has been contributed to by US Government employees and their work is in the public domain in the USA.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4530-ceb32099dce550d90994199d9b0650c108bbcfe940e657c1ed5d84ae6c971f893</citedby><cites>FETCH-LOGICAL-c4530-ceb32099dce550d90994199d9b0650c108bbcfe940e657c1ed5d84ae6c971f893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Falz.12610$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Falz.12610$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,550,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35234334$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:148977607$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Lecca, Daniela</creatorcontrib><creatorcontrib>Jung, Yoo Jin</creatorcontrib><creatorcontrib>Scerba, Michael T.</creatorcontrib><creatorcontrib>Hwang, Inho</creatorcontrib><creatorcontrib>Kim, Yu Kyung</creatorcontrib><creatorcontrib>Kim, Sun</creatorcontrib><creatorcontrib>Modrow, Sydney</creatorcontrib><creatorcontrib>Tweedie, David</creatorcontrib><creatorcontrib>Hsueh, Shih‐Chang</creatorcontrib><creatorcontrib>Liu, Dong</creatorcontrib><creatorcontrib>Luo, Weiming</creatorcontrib><creatorcontrib>Glotfelty, Elliot</creatorcontrib><creatorcontrib>Li, Yazhou</creatorcontrib><creatorcontrib>Wang, Jia‐Yi</creatorcontrib><creatorcontrib>Luo, Yu</creatorcontrib><creatorcontrib>Hoffer, Barry J.</creatorcontrib><creatorcontrib>Kim, Dong Seok</creatorcontrib><creatorcontrib>McDevitt, Ross A.</creatorcontrib><creatorcontrib>Greig, Nigel H.</creatorcontrib><title>Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis</title><title>Alzheimer's & dementia</title><addtitle>Alzheimers Dement</addtitle><description>Objective
Evaluating the efficacy of 3,6’‐dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline.
Background
Amyloid‐β (Aβ) or tau‐focused clinical trials have proved unsuccessful in mitigating AD‐associated cognitive impairment. Identification of new drug targets is needed. Neuroinflammation is a therapeutic target in neurodegenerative disorders, and TNF‐α a pivotal neuroinflammatory driver.
New hypothesis
AD‐associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aβ generation will define the role of neuroinflammation in AD progression.
Major challenges
Difficulty of TNF‐α‐lowering compounds reaching brain, and identification of a therapeutic‐time window to preserve the beneficial role of neuroinflammatory processes.
Linkage to other major theories
Microglia/astroglia are heavily implicated in maintenance of synaptic plasticity/function in healthy brain and are disrupted by Aβ. Mitigation of chronic gliosis can restore synaptic homeostasis/cognitive function.</description><subject>3,6’‐dithioPomalidomide</subject><subject>5xFAD mice</subject><subject>Alzheimer Disease</subject><subject>Alzheimer pathology</subject><subject>Amyloid beta-Peptides</subject><subject>amyloid hypothesis</subject><subject>Animals</subject><subject>Cognition</subject><subject>Cognitive Dysfunction</subject><subject>Disease Models, Animal</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Microglia</subject><subject>microglial/astrocyte activation</subject><subject>neuroinflammation</subject><subject>Neuroinflammatory Diseases</subject><subject>Neuronal Plasticity</subject><subject>TNF‐α</subject><subject>Tumor Necrosis Factor-alpha</subject><issn>1552-5260</issn><issn>1552-5279</issn><issn>1552-5279</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp1kcFO3DAQhq0KVCj00BeofIRDYJzY2TUHpNWqpZVWQkLtgV4sx5mwbh17iRPQ9unxkmUFB04ez3z-Z8Y_IV8YnDGA_Fy7_2csLxl8IIdMiDwT-UTu7eISDsinGP8CcJgy8ZEcFCIveFHwQ3J7ExzS0FCz7IK3hnocumB943Tb6t4GT60fkyunY2-N7ddU-5qacOdtbx-QNoM3G_KCzuhyvQr9EqONx2S_0S7i5-15RH5___Zr_iNbXF_9nM8WmeGigMxgVeQgZW1QCKhlCjlLV1lBKcAwmFaVaVBywFJMDMNa1FOusTRywpqpLI5INurGR1wNlVp1ttXdWgVt1Tb1L0WouBDpkxJ_OfKp0mJq6_tOuzfP3la8Xaq78KAkLyaMQxI42Qp04X7A2KvWRoPOaY9hiCr1EPlmt81spyNquhBjh82uDQO1sU4l69SzdYn9-nquHfniVQLOR-DROly_r6Rmiz-j5BOFdaXo</recordid><startdate>202211</startdate><enddate>202211</enddate><creator>Lecca, Daniela</creator><creator>Jung, Yoo Jin</creator><creator>Scerba, Michael T.</creator><creator>Hwang, Inho</creator><creator>Kim, Yu Kyung</creator><creator>Kim, Sun</creator><creator>Modrow, Sydney</creator><creator>Tweedie, David</creator><creator>Hsueh, Shih‐Chang</creator><creator>Liu, Dong</creator><creator>Luo, Weiming</creator><creator>Glotfelty, Elliot</creator><creator>Li, Yazhou</creator><creator>Wang, Jia‐Yi</creator><creator>Luo, Yu</creator><creator>Hoffer, Barry J.</creator><creator>Kim, Dong Seok</creator><creator>McDevitt, Ross A.</creator><creator>Greig, Nigel H.</creator><general>John Wiley and Sons Inc</general><scope>24P</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>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>202211</creationdate><title>Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis</title><author>Lecca, Daniela ; Jung, Yoo Jin ; Scerba, Michael T. ; Hwang, Inho ; Kim, Yu Kyung ; Kim, Sun ; Modrow, Sydney ; Tweedie, David ; Hsueh, Shih‐Chang ; Liu, Dong ; Luo, Weiming ; Glotfelty, Elliot ; Li, Yazhou ; Wang, Jia‐Yi ; Luo, Yu ; Hoffer, Barry J. ; Kim, Dong Seok ; McDevitt, Ross A. ; Greig, Nigel H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4530-ceb32099dce550d90994199d9b0650c108bbcfe940e657c1ed5d84ae6c971f893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>3,6’‐dithioPomalidomide</topic><topic>5xFAD mice</topic><topic>Alzheimer Disease</topic><topic>Alzheimer pathology</topic><topic>Amyloid beta-Peptides</topic><topic>amyloid hypothesis</topic><topic>Animals</topic><topic>Cognition</topic><topic>Cognitive Dysfunction</topic><topic>Disease Models, Animal</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Microglia</topic><topic>microglial/astrocyte activation</topic><topic>neuroinflammation</topic><topic>Neuroinflammatory Diseases</topic><topic>Neuronal Plasticity</topic><topic>TNF‐α</topic><topic>Tumor Necrosis Factor-alpha</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lecca, Daniela</creatorcontrib><creatorcontrib>Jung, Yoo Jin</creatorcontrib><creatorcontrib>Scerba, Michael T.</creatorcontrib><creatorcontrib>Hwang, Inho</creatorcontrib><creatorcontrib>Kim, Yu Kyung</creatorcontrib><creatorcontrib>Kim, Sun</creatorcontrib><creatorcontrib>Modrow, Sydney</creatorcontrib><creatorcontrib>Tweedie, David</creatorcontrib><creatorcontrib>Hsueh, Shih‐Chang</creatorcontrib><creatorcontrib>Liu, Dong</creatorcontrib><creatorcontrib>Luo, Weiming</creatorcontrib><creatorcontrib>Glotfelty, Elliot</creatorcontrib><creatorcontrib>Li, Yazhou</creatorcontrib><creatorcontrib>Wang, Jia‐Yi</creatorcontrib><creatorcontrib>Luo, Yu</creatorcontrib><creatorcontrib>Hoffer, Barry J.</creatorcontrib><creatorcontrib>Kim, Dong Seok</creatorcontrib><creatorcontrib>McDevitt, Ross A.</creatorcontrib><creatorcontrib>Greig, Nigel H.</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Alzheimer's & dementia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lecca, Daniela</au><au>Jung, Yoo Jin</au><au>Scerba, Michael T.</au><au>Hwang, Inho</au><au>Kim, Yu Kyung</au><au>Kim, Sun</au><au>Modrow, Sydney</au><au>Tweedie, David</au><au>Hsueh, Shih‐Chang</au><au>Liu, Dong</au><au>Luo, Weiming</au><au>Glotfelty, Elliot</au><au>Li, Yazhou</au><au>Wang, Jia‐Yi</au><au>Luo, Yu</au><au>Hoffer, Barry J.</au><au>Kim, Dong Seok</au><au>McDevitt, Ross A.</au><au>Greig, Nigel H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis</atitle><jtitle>Alzheimer's & dementia</jtitle><addtitle>Alzheimers Dement</addtitle><date>2022-11</date><risdate>2022</risdate><volume>18</volume><issue>11</issue><spage>2327</spage><epage>2340</epage><pages>2327-2340</pages><issn>1552-5260</issn><issn>1552-5279</issn><eissn>1552-5279</eissn><abstract>Objective
Evaluating the efficacy of 3,6’‐dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline.
Background
Amyloid‐β (Aβ) or tau‐focused clinical trials have proved unsuccessful in mitigating AD‐associated cognitive impairment. Identification of new drug targets is needed. Neuroinflammation is a therapeutic target in neurodegenerative disorders, and TNF‐α a pivotal neuroinflammatory driver.
New hypothesis
AD‐associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aβ generation will define the role of neuroinflammation in AD progression.
Major challenges
Difficulty of TNF‐α‐lowering compounds reaching brain, and identification of a therapeutic‐time window to preserve the beneficial role of neuroinflammatory processes.
Linkage to other major theories
Microglia/astroglia are heavily implicated in maintenance of synaptic plasticity/function in healthy brain and are disrupted by Aβ. Mitigation of chronic gliosis can restore synaptic homeostasis/cognitive function.</abstract><cop>United States</cop><pub>John Wiley and Sons Inc</pub><pmid>35234334</pmid><doi>10.1002/alz.12610</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1552-5260 |
| ispartof | Alzheimer's & dementia, 2022-11, Vol.18 (11), p.2327-2340 |
| issn | 1552-5260 1552-5279 1552-5279 |
| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; SWEPUB Freely available online |
| subjects | 3,6’‐dithioPomalidomide 5xFAD mice Alzheimer Disease Alzheimer pathology Amyloid beta-Peptides amyloid hypothesis Animals Cognition Cognitive Dysfunction Disease Models, Animal Mice Mice, Inbred C57BL Mice, Transgenic Microglia microglial/astrocyte activation neuroinflammation Neuroinflammatory Diseases Neuronal Plasticity TNF‐α Tumor Necrosis Factor-alpha |
| title | Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis |
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