Functional insights from biophysical study of TREM2 interactions with apoE and Aβ(1-42).
Functional insights from biophysical study of TREM2 interactions with apoE and Aβ(1-42).
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DOI：
10.1002/alz.12194
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发表时间：
2020-10-08
期刊：
影响因子：
--
通讯作者：
Brett TJ
中科院分区：
文献类型：
--
作者：
Kober DL;Stuchell-Brereton MD;Kluender CE;Dean HB;Strickland MR;Steinberg DF;Nelson SS;Baban B;Holtzman DM;Frieden C;Alexander-Brett J;Roberson ED;Song Y;Brett TJ
TREM2 is an immune receptor expressed on microglia that also can become soluble (sTREM2). How TREM2 engages different ligands remains poorly understood. We used comprehensive BLI analysis to investigate TREM2 and sTREM2 interactions with ApoE and monomeric Aβ (mAβ42). TREM2 engagement of ApoE was protein mediated with little effect of lipidation, showing slight affinity differences between isoforms (E4 > E3 > E2). Another family member, TREML2, didn’t bind ApoE. Disease-linked TREM2 variants within a “basic patch” minimally impact ApoE binding. Instead, TREM2 uses a unique hydrophobic surface to bind ApoE, which requires the ApoE hinge region. TREM2 and sTREM2 directly bind mAβ42 and potently inhibit Aβ42 polymerization, suggesting a potential role for soluble sTREM2 in preventing AD pathogenesis. These findings demonstrate that TREM2 has at least two ligand-binding surfaces that might be therapeutic targets and uncovers a potential function for sTREM2 in directly inhibiting Aβ polymerization.
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影响因子：
2.9
作者：
Garai, Kanchan;Verghese, Philip B.;Baban, Berevan;Holtzman, David M.;Frieden, Carl
通讯作者：
Frieden, Carl
DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
影响因子：
3.4
作者：
Dean, Hunter B.;Roberson, Erik D.;Song, Yuhua
通讯作者：
Song, Yuhua
影响因子：
2.9
作者：
Garai, Kanchan;Baban, Berevan;Frieden, Carl
通讯作者：
Frieden, Carl
影响因子：
4.2
作者：
Benitez BA;Jin SC;Guerreiro R;Graham R;Lord J;Harold D;Sims R;Lambert JC;Gibbs JR;Bras J;Sassi C;Harari O;Bertelsen S;Lupton MK;Powell J;Bellenguez C;Brown K;Medway C;Haddick PC;van der Brug MP;Bhangale T;Ortmann W;Behrens T;Mayeux R;Pericak-Vance MA;Farrer LA;Schellenberg GD;Haines JL;Turton J;Braae A;Barber I;Fagan AM;Holtzman DM;Morris JC;3C Study Group;EADI consortium;Alzheimer's Disease Genetic Consortium (ADGC);Alzheimer's Disease Neuroimaging Initiative (ADNI);GERAD Consortium;Williams J;Kauwe JS;Amouyel P;Morgan K;Singleton A;Hardy J;Goate AM;Cruchaga C
通讯作者：
Cruchaga C