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000165614 1001_ $$aZambusi, Alessandro$$b0
000165614 245__ $$aTDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury.
000165614 260__ $$aNew York, NY$$bNature America$$c2022
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000165614 520__ $$aDecreasing the activation of pathology-activated microglia is crucial to prevent chronic inflammation and tissue scarring. In this study, we used a stab wound injury model in zebrafish and identified an injury-induced microglial state characterized by the accumulation of lipid droplets and TAR DNA-binding protein of 43 kDa (TDP-43)+ condensates. Granulin-mediated clearance of both lipid droplets and TDP-43+ condensates was necessary and sufficient to promote the return of microglia back to the basal state and achieve scarless regeneration. Moreover, in postmortem cortical brain tissues from patients with traumatic brain injury, the extent of microglial activation correlated with the accumulation of lipid droplets and TDP-43+ condensates. Together, our results reveal a mechanism required for restoring microglia to a nonactivated state after injury, which has potential for new therapeutic applications in humans.
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000165614 650_7 $$2NLM Chemicals$$aDNA-Binding Proteins
000165614 650_2 $$2MeSH$$aHumans
000165614 650_2 $$2MeSH$$aAnimals
000165614 650_2 $$2MeSH$$aMicroglia
000165614 650_2 $$2MeSH$$aLipid Droplets
000165614 650_2 $$2MeSH$$aZebrafish
000165614 650_2 $$2MeSH$$aBrain Injuries, Traumatic
000165614 650_2 $$2MeSH$$aDNA-Binding Proteins
000165614 650_2 $$2MeSH$$aRegeneration
000165614 7001_ $$aNovoselc, Klara Tereza$$b1
000165614 7001_ $$aHutten, Saskia$$b2
000165614 7001_ $$aKalpazidou, Sofia$$b3
000165614 7001_ $$00000-0002-8352-1498$$aKoupourtidou, Christina$$b4
000165614 7001_ $$aSchieweck, Rico$$b5
000165614 7001_ $$0P:(DE-2719)2812151$$aAschenbroich, Sven$$b6$$udzne
000165614 7001_ $$aSilva, Lara$$b7
000165614 7001_ $$00000-0001-8485-9653$$aYazgili, Ayse Seda$$b8
000165614 7001_ $$0P:(DE-2719)9000319$$avan Bebber, Frauke$$b9$$udzne
000165614 7001_ $$0P:(DE-2719)2241638$$aSchmid, Bettina$$b10$$udzne
000165614 7001_ $$00000-0002-8731-4330$$aMöller, Gabriel$$b11
000165614 7001_ $$aTritscher, Clara$$b12
000165614 7001_ $$00000-0001-6941-2669$$aStigloher, Christian$$b13
000165614 7001_ $$aDelbridge, Claire$$b14
000165614 7001_ $$00000-0001-5950-616X$$aSirko, Swetlana$$b15
000165614 7001_ $$0P:(DE-2719)2812248$$aGünes, Zeynep Irem$$b16$$udzne
000165614 7001_ $$0P:(DE-2719)9000187$$aLiebscher, Sabine$$b17$$udzne
000165614 7001_ $$aSchlegel, Jürgen$$b18
000165614 7001_ $$aAliee, Hananeh$$b19
000165614 7001_ $$00000-0002-2419-1943$$aTheis, Fabian$$b20
000165614 7001_ $$aMeiners, Silke$$b21
000165614 7001_ $$aKiebler, Michael$$b22
000165614 7001_ $$0P:(DE-2719)9000059$$aDormann, Dorothee$$b23$$udzne
000165614 7001_ $$00000-0002-4381-0041$$aNinkovic, Jovica$$b24
000165614 773__ $$0PERI:(DE-600)1494955-6$$a10.1038/s41593-022-01199-y$$gVol. 25, no. 12, p. 1608 - 1625$$n12$$p1608 - 1625$$tNature neuroscience$$v25$$x1097-6256$$y2022
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