140482 20240321220822.0 10.15252/emmm.201809665 doi pmid:30617153 pmid pmc:PMC6365929 pmc 1715-4684 ISSN 1757-4676 ISSN 1757-4684 ISSN altmetric:53595424 altmetric DZNE-2020-06804 English 610 Reichenbach, Nicole P:(DE-2719)2811281 0 First author Inhibition of Stat3-mediated astrogliosis ameliorates pathology in an Alzheimer's disease model. Heidelberg 2019 EMBO Press online Crossref EMBO 2019-01-07 print Crossref EMBO 2019-02-01 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1708432762_6808 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Reactive astrogliosis is a hallmark of Alzheimer's disease (AD), but its role for disease initiation and progression has remained incompletely understood. We here show that the transcription factor Stat3 (signal transducer and activator of transcription 3), a canonical inducer of astrogliosis, is activated in an AD mouse model and human AD Therefore, using a conditional knockout approach, we deleted Stat3 specifically in astrocytes in the APP/PS1 model of AD We found that Stat3-deficient APP/PS1 mice show decreased β-amyloid levels and plaque burden. Plaque-close microglia displayed a more complex morphology, internalized more β-amyloid, and upregulated amyloid clearance pathways in Stat3-deficient mice. Moreover, astrocyte-specific Stat3-deficient APP/PS1 mice showed decreased pro-inflammatory cytokine activation and lower dystrophic neurite burden, and were largely protected from cerebral network imbalance. Finally, Stat3 deletion in astrocytes also strongly ameliorated spatial learning and memory decline in APP/PS1 mice. Importantly, these protective effects on network dysfunction and cognition were recapitulated in APP/PS1 mice systemically treated with a preclinical Stat3 inhibitor drug. In summary, our data implicate Stat3-mediated astrogliosis as an important therapeutic target in AD. 341 - Molecular Signaling (POF3-341) G:(DE-HGF)POF3-341 POF3-341 POF III 0 342 - Disease Mechanisms and Model Systems (POF3-342) G:(DE-HGF)POF3-342 POF3-342 POF III 1 344 - Clinical and Health Care Research (POF3-344) G:(DE-HGF)POF3-344 POF3-344 POF III 2 2019-01-07 Crossref http://creativecommons.org/licenses/by/4.0/ 2019-01-07 Crossref http://doi.wiley.com/10.1002/tdm_license_1.1 Dataset connected to CrossRef, PubMed, STAT3 Transcription Factor NLM Chemicals STAT3 protein, human NLM Chemicals Stat3 protein, mouse NLM Chemicals Alzheimer Disease: pathology MeSH Animals MeSH Astrocytes: pathology MeSH Cell Proliferation MeSH Disease Models, Animal MeSH Gene Knockout Techniques MeSH Humans MeSH Mice MeSH Mice, Knockout MeSH STAT3 Transcription Factor: analysis MeSH STAT3 Transcription Factor: deficiency MeSH Delekate, Andrea P:(DE-2719)2810454 1 Plescher, Monika P:(DE-2719)2812070 2 Schmitt, Franziska P:(DE-2719)2812206 3 Krauß, Sybille P:(DE-2719)2421562 4 Blank, Nelli P:(DE-2719)2811722 5 Halle, Annett P:(DE-2719)2812038 6 Petzold, Gabor C P:(DE-2719)2810273 7 Last author 10.15252/emmm.201809665 : EMBO, 2019-01-07 2 journal-article Crossref EMBO Molecular Medicine 11 2019 1757-4676 10.15252/emmm.201809665 Vol. 11, no. 2 PERI:(DE-600)2485479-7 2 11:2 e9665 EMBO molecular medicine 11 2019 1757-4676 OpenAccess http://pub.dzne.de/record/140482/files/DZNE-2020-06804.pdf OpenAccess pdfa http://pub.dzne.de/record/140482/files/DZNE-2020-06804.pdf?subformat=pdfa Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365929 oai:pub.dzne.de:140482 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)2811281 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2810454 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2812070 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2812206 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 4 P:(DE-2719)2421562 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 5 P:(DE-2719)2811722 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 6 P:(DE-2719)2812038 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 7 P:(DE-2719)2810273 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-341 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Molecular Signaling 0 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-342 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Disease Mechanisms and Model Systems 1 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-344 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Clinical and Health Care Research 2 2019 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-29 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-29 Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC JCR StatID:(DE-HGF)0100 StatID EMBO MOL MED : 2021 2022-11-29 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2021-07-19T13:19:31Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2021-07-19T13:19:31Z IF >= 10 StatID:(DE-HGF)9910 StatID EMBO MOL MED : 2021 2022-11-29 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-29 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Blind peer review, Double blind peer review 2021-07-19T13:19:31Z DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-29 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-29 I:(DE-2719)1013020 AG Petzold ; AG Petzold Vascular Neurology 0 I:(DE-2719)1013003 AG Bano Aging and Neurodegeneration 1 I:(DE-2719)1011006 AG Krauß Regulatory RNA-protein interaction in neurodegenerative diseases 2 I:(DE-2719)1013034 AG Halle Microglia and Neuroinflammation 3 journal VDB UNRESTRICTED I:(DE-2719)1013020 I:(DE-2719)1013003 I:(DE-2719)1011006 I:(DE-2719)1013034 FullTexts -- missing cx lookup -- 10.1128/MCB.21.5.1621-1632.2001 Crossref 10.1128/MCB.21.5.1621-1632.2001 -- missing cx lookup -- 10.1016/j.neuron.2008.10.013 Crossref 10.1016/j.neuron.2008.10.013 -- missing cx lookup -- 10.1523/JNEUROSCI.3516-14.2015 Crossref 10.1523/JNEUROSCI.3516-14.2015 -- missing cx lookup -- 10.1016/j.neuron.2013.12.034 Crossref 10.1016/j.neuron.2013.12.034 -- missing cx lookup -- 10.2967/jnumed.110.087031 Crossref 10.2967/jnumed.110.087031 -- missing cx lookup -- 10.1186/s40478-018-0606-1 Crossref 10.1186/s40478-018-0606-1 -- missing cx lookup -- 10.1038/ncomms7176 Crossref 10.1038/ncomms7176 -- missing cx lookup -- 10.1038/ncomms6422 Crossref 10.1038/ncomms6422 -- missing cx lookup -- 10.1016/j.yjmcc.2003.10.006 Crossref 10.1016/j.yjmcc.2003.10.006 -- missing cx lookup -- 10.3758/BF03193146 Crossref 10.3758/BF03193146 -- missing cx lookup -- 10.1021/ml4003138 Crossref 10.1021/ml4003138 -- missing cx lookup -- 10.1016/S1474-4422(15)70016-5 Crossref 10.1016/S1474-4422(15)70016-5 -- missing cx lookup -- 10.1523/JNEUROSCI.1709-08.2008 Crossref 10.1523/JNEUROSCI.1709-08.2008 -- missing cx lookup -- 10.1111/jnc.13490 Crossref 10.1111/jnc.13490 -- missing cx lookup -- 10.1093/hmg/ddh019 Crossref 10.1093/hmg/ddh019 -- missing cx lookup -- 10.1002/(SICI)1098-1136(200005)30:3<253::AID-GLIA5>3.0.CO;2-O Crossref 10.1002/(SICI)1098-1136(200005)30:3<253::AID-GLIA5>3.0.CO;2-O -- missing cx lookup -- 10.1073/pnas.1300378110 Crossref 10.1073/pnas.1300378110 -- missing cx lookup -- 10.1038/nature21029 Crossref 10.1038/nature21029 -- missing cx lookup -- 10.1016/j.neuron.2018.10.031 Crossref 10.1016/j.neuron.2018.10.031 -- missing cx lookup -- 10.1038/nm1425 Crossref 10.1038/nm1425 -- missing cx lookup -- 10.1038/nn.2535 Crossref 10.1038/nn.2535 -- missing cx lookup -- 10.1038/nrn.2016.141 Crossref 10.1038/nrn.2016.141 -- missing cx lookup -- 10.1182/blood-2006-02-003012 Crossref 10.1182/blood-2006-02-003012 -- missing cx lookup -- 10.1152/physrev.00041.2013 Crossref 10.1152/physrev.00041.2013 -- missing cx lookup -- 10.1007/s00401-015-1513-1 Crossref 10.1007/s00401-015-1513-1 -- missing cx lookup -- 10.1073/pnas.1117218109 Crossref 10.1073/pnas.1117218109 -- missing cx lookup -- 10.1172/JCI89354 Crossref 10.1172/JCI89354 -- missing cx lookup -- 10.1084/jem.20171487 Crossref 10.1084/jem.20171487 -- missing cx lookup -- 10.1038/s41586-018-0119-x Crossref 10.1038/s41586-018-0119-x -- missing cx lookup -- 10.1016/j.neuron.2012.03.026 Crossref 10.1016/j.neuron.2012.03.026 2014 Crossref Schafer DP 2014 -- missing cx lookup -- 10.1126/scitranslmed.aaf6295 Crossref 10.1126/scitranslmed.aaf6295 -- missing cx lookup -- 10.1038/nn.3691 Crossref 10.1038/nn.3691 -- missing cx lookup -- 10.1038/s41467-017-01283-z Crossref 10.1038/s41467-017-01283-z -- missing cx lookup -- 10.1016/S1474-4422(10)70325-2 Crossref 10.1016/S1474-4422(10)70325-2 -- missing cx lookup -- 10.1038/ni.3691 Crossref 10.1038/ni.3691 -- missing cx lookup -- 10.1038/nprot.2006.116 Crossref 10.1038/nprot.2006.116 -- missing cx lookup -- 10.1007/s12264-018-0262-2 Crossref 10.1007/s12264-018-0262-2 -- missing cx lookup -- 10.1016/j.neuroscience.2006.06.034 Crossref 10.1016/j.neuroscience.2006.06.034 -- missing cx lookup -- 10.1007/s11064-011-0576-1 Crossref 10.1007/s11064-011-0576-1 -- missing cx lookup -- 10.1038/s41591-018-0051-5 Crossref 10.1038/s41591-018-0051-5 -- missing cx lookup -- 10.1523/JNEUROSCI.6221-11.2012 Crossref 10.1523/JNEUROSCI.6221-11.2012