An intracellular threonine of amyloid-β precursor protein mediates synaptic plasticity deficits and memory loss.
An intracellular threonine of amyloid-β precursor protein mediates synaptic plasticity deficits and memory loss.
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DOI：
10.1371/journal.pone.0057120
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
D'Adamio L
中科院分区：
文献类型：
--
作者：
Lombino F;Biundo F;Tamayev R;Arancio O;D'Adamio L
Mutations in Amyloid-ß Precursor Protein (APP) and BRI2/ITM2b genes cause Familial Alzheimer and Danish Dementias (FAD/FDD), respectively. APP processing by BACE1, which is inhibited by BRI2, yields sAPPß and ß-CTF. ß-CTF is cleaved by gamma-secretase to produce Aß. A knock-in mouse model of FDD, called FDDKI, shows deficits in memory and synaptic plasticity, which can be attributed to sAPPß/ß-CTF but not Aß. We have investigated further the pathogenic function of ß-CTF focusing on Thr668 of ß-CTF because phosphorylation of Thr668 is increased in AD cases. We created a knock-in mouse bearing a Thr668Ala mutation (APPTA mice) that prevents phosphorylation at this site. This mutation prevents the development of memory and synaptic plasticity deficits in FDDKI mice. These data are consistent with a role for the carboxyl-terminal APP domain in the pathogenesis of dementia and suggest that averting the noxious role of Thr668 is a viable therapeutic strategy for human dementias.
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影响因子：
3.7
作者：
Barbagallo AP;Weldon R;Tamayev R;Zhou D;Giliberto L;Foreman O;D'Adamio L
通讯作者：
D'Adamio L
影响因子：
64.8
作者：
Israel, Mason A.;Yuan, Shauna H.;Bardy, Cedric;Reyna, Sol M.;Mu, Yangling;Herrera, Cheryl;Hefferan, Michael P.;Van Gorp, Sebastiaan;Nazor, Kristopher L.;Boscolo, Francesca S.;Carson, Christian T.;Laurent, Louise C.;Marsala, Martin;Gage, Fred H.;Remes, Anne M.;Koo, Edward H.;Goldstein, Lawrence S. B.
通讯作者：
Goldstein, Lawrence S. B.
影响因子：
7.8
作者：
Matrone C;Luvisetto S;La Rosa LR;Tamayev R;Pignataro A;Canu N;Yang L;Barbagallo AP;Biundo F;Lombino F;Zheng H;Ammassari-Teule M;D'Adamio L
通讯作者：
D'Adamio L
影响因子：
4.8
作者：
Fotinopoulou, A;Tsachaki, M;Efthimiopoulos, S
通讯作者：
Efthimiopoulos, S
影响因子：
5.3
作者：
Matsuda, Shuji;Giliberto, Luca;D'Adamio, Luciano
通讯作者：
D'Adamio, Luciano