Keane, Lily;
Antignano, Ignazio;
Riechers, Sean-Patrick;
Zollinger, Raphael;
Dumas, Anaelle A;
Offermann, Nina;
Bernis, Maria E;
... Capasso, Melania; + view all
(2021)
mTOR-dependent translation amplifies microglia priming in aging mice.
Journal of Clinical Investigation
, 131
(1)
, Article e132727. 10.1172/JCI132727.
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Abstract
Microglia maintain homeostasis in the brain. However, with age, they become primed and respond more strongly to inflammatory stimuli. We show here that microglia from aged mice had upregulated mTOR complex 1 signaling controlling translation, as well as protein levels of inflammatory mediators. Genetic ablation of mTOR signaling showed a dual yet contrasting effect on microglia priming: It caused an NF-κB-dependent upregulation of priming genes at the mRNA level; however, mice displayed reduced cytokine protein levels, diminished microglia activation, and milder sickness behavior. The effect on translation was dependent on reduced phosphorylation of 4EBP1, resulting in decreased binding of eIF4E to eIF4G. Similar changes were present in aged human microglia and in damage-associated microglia, indicating that upregulation of mTOR-dependent translation is an essential aspect of microglia priming in aging and neurodegeneration.
| Type: | Article |
|---|---|
| Title: | mTOR-dependent translation amplifies microglia priming in aging mice |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1172/JCI132727 |
| Publisher version: | https://doi.org/10.1172/JCI132727 |
| Language: | English |
| Additional information: | This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Medicine, Research & Experimental, Research & Experimental Medicine, INITIATION-FACTOR 4E, PROTEIN-SYNTHESIS, MAMMALIAN TARGET, LIFE-SPAN, COMPLEX 1, PHOSPHORYLATION, KINASE, EIF4E, RHEB, BINDING |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10165034 |
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