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@ARTICLE{Zambusi:165614,
author = {Zambusi, Alessandro and Novoselc, Klara Tereza and Hutten,
Saskia and Kalpazidou, Sofia and Koupourtidou, Christina and
Schieweck, Rico and Aschenbroich, Sven and Silva, Lara and
Yazgili, Ayse Seda and van Bebber, Frauke and Schmid,
Bettina and Möller, Gabriel and Tritscher, Clara and
Stigloher, Christian and Delbridge, Claire and Sirko,
Swetlana and Günes, Zeynep Irem and Liebscher, Sabine and
Schlegel, Jürgen and Aliee, Hananeh and Theis, Fabian and
Meiners, Silke and Kiebler, Michael and Dormann, Dorothee
and Ninkovic, Jovica},
title = {{TDP}-43 condensates and lipid droplets regulate the
reactivity of microglia and regeneration after traumatic
brain injury.},
journal = {Nature neuroscience},
volume = {25},
number = {12},
issn = {1097-6256},
address = {New York, NY},
publisher = {Nature America},
reportid = {DZNE-2022-01747},
pages = {1608 - 1625},
year = {2022},
abstract = {Decreasing the activation of pathology-activated microglia
is crucial to prevent chronic inflammation and tissue
scarring. In this study, we used a stab wound injury model
in zebrafish and identified an injury-induced microglial
state characterized by the accumulation of lipid droplets
and TAR DNA-binding protein of 43 kDa (TDP-43)+ condensates.
Granulin-mediated clearance of both lipid droplets and
TDP-43+ condensates was necessary and sufficient to promote
the return of microglia back to the basal state and achieve
scarless regeneration. Moreover, in postmortem cortical
brain tissues from patients with traumatic brain injury, the
extent of microglial activation correlated with the
accumulation of lipid droplets and TDP-43+ condensates.
Together, our results reveal a mechanism required for
restoring microglia to a nonactivated state after injury,
which has potential for new therapeutic applications in
humans.},
keywords = {Humans / Animals / Microglia / Lipid Droplets / Zebrafish /
Brain Injuries, Traumatic / DNA-Binding Proteins /
Regeneration / DNA-Binding Proteins (NLM Chemicals)},
cin = {AG Schmid München},
ddc = {610},
cid = {I:(DE-2719)1140002},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36424432},
doi = {10.1038/s41593-022-01199-y},
url = {https://pub.dzne.de/record/165614},
}