% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Reichenbach:140482,
author = {Reichenbach, Nicole and Delekate, Andrea and Plescher,
Monika and Schmitt, Franziska and Krauß, Sybille and Blank,
Nelli and Halle, Annett and Petzold, Gabor C},
title = {{I}nhibition of {S}tat3-mediated astrogliosis ameliorates
pathology in an {A}lzheimer's disease model.},
journal = {EMBO molecular medicine},
volume = {11},
number = {2},
issn = {1757-4676},
address = {Heidelberg},
publisher = {EMBO Press},
reportid = {DZNE-2020-06804},
pages = {e9665},
year = {2019},
abstract = {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.},
keywords = {Alzheimer Disease: pathology / Animals / Astrocytes:
pathology / Cell Proliferation / Disease Models, Animal /
Gene Knockout Techniques / Humans / Mice / Mice, Knockout /
STAT3 Transcription Factor: analysis / STAT3 Transcription
Factor: deficiency / STAT3 Transcription Factor (NLM
Chemicals) / STAT3 protein, human (NLM Chemicals) / Stat3
protein, mouse (NLM Chemicals)},
cin = {AG Petzold ; AG Petzold / AG Bano / AG Krauß / AG Halle},
ddc = {610},
cid = {I:(DE-2719)1013020 / I:(DE-2719)1013003 /
I:(DE-2719)1011006 / I:(DE-2719)1013034},
pnm = {341 - Molecular Signaling (POF3-341) / 342 - Disease
Mechanisms and Model Systems (POF3-342) / 344 - Clinical and
Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-341 / G:(DE-HGF)POF3-342 /
G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30617153},
pmc = {pmc:PMC6365929},
doi = {10.15252/emmm.201809665},
url = {https://pub.dzne.de/record/140482},
}