339 Bridgeside Point
Emilie Castranio will present on the article - "TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model"
EOH Journal Club Seminar - Spring 2016 Date: Thursday January 21, 2016 Time: 11am - 12pm Presenter: Emilie Castranio Paper: TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model Authors: Wang Y, Cella M, Mallinson K, Ulrich JD, Young KL, Robinette ML, Gilfillan S, Krishnan GM, Sudhakar S, Zinselmeyer BH, Holtzman DM, Cirrito JR, Colonna M Abstract: Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor that triggers intracellular protein tyrosine phosphorylation. Recent genome-wide association studies have shown that a rare R47H mutation of TREM2 correlates with a substantial increase in the risk of developing Alzheimer's disease (AD). To address the basis for this genetic association, we studied TREM2 deficiency in the 5XFAD mouse model of AD. We found that TREM2 deficiency and haploinsufficiency augment β-amyloid (Aβ) accumulation due to a dysfunctional response of microglia, which fail to cluster around Aβ plaques and become apoptotic. We further demonstrate that TREM2 senses a broad array of anionic and zwitterionic lipids known to associate with fibrillar Aβ in lipid membranes and to be exposed on the surface of damaged neurons. Remarkably, the R47H mutation impairs TREM2 detection of lipid ligands. Thus, TREM2 detects damage-associated lipid patterns associated with neurodegeneration, sustaining the microglial response to Aβ accumulation.
Last Updated On Monday, March 21, 2016 by GSPH Webmaster
Created On Monday, March 21, 2016
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