Plate IV.216 · Publications
TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury
Article in Nature Neuroscience, 24 November 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.
Cite
@article{zambusi2022tdp,
title = {{TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury}},
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},
journal = {Nature Neuroscience},
publisher = {Springer Science and Business Media LLC},
year = {2022},
month = nov,
doi = {10.1038/s41593-022-01199-y},
url = {https://doi.org/10.1038/s41593-022-01199-y},
pmid = {36424432}
}