Restored glial glutamate transporter EAAT2 function as a potential therapeutic approach for Alzheimer's disease.
Restored glial glutamate transporter EAAT2 function as a potential therapeutic approach for Alzheimer's disease.
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DOI：
10.1084/jem.20140413
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发表时间：
2015-03-09
期刊：
影响因子：
--
通讯作者：
Lin CL
中科院分区：
文献类型：
--
作者：
Takahashi K;Kong Q;Lin Y;Stouffer N;Schulte DA;Lai L;Liu Q;Chang LC;Dominguez S;Xing X;Cuny GD;Hodgetts KJ;Glicksman MA;Lin CL
Takahashi et al. demonstrate that restoring glial glutamate transporter EAAT2 function improves cognitive functions and synaptic integrity while reducing amyloid plaques in a sustained fashion after treatment cessation. Glutamatergic systems play a critical role in cognitive functions and are known to be defective in Alzheimer’s disease (AD) patients. Previous literature has indicated that glial glutamate transporter EAAT2 plays an essential role in cognitive functions and that loss of EAAT2 protein is a common phenomenon observed in AD patients and animal models. In the current study, we investigated whether restored EAAT2 protein and function could benefit cognitive functions and pathology in APPSw,Ind mice, an animal model of AD. A transgenic mouse approach via crossing EAAT2 transgenic mice with APPSw,Ind. mice and a pharmacological approach using a novel EAAT2 translational activator, LDN/OSU-0212320, were conducted. Findings from both approaches demonstrated that restored EAAT2 protein function significantly improved cognitive functions, restored synaptic integrity, and reduced amyloid plaques. Importantly, the observed benefits were sustained one month after compound treatment cessation, suggesting that EAAT2 is a potential disease modifier with therapeutic potential for AD.
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DOI：
10.1523/jneurosci.0203-11.2011
发表时间：
2011-05-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Li S;Jin M;Koeglsperger T;Shepardson NE;Shankar GM;Selkoe DJ
通讯作者：
Selkoe DJ
影响因子：
4.2
作者：
Kabogo, D.;Rauw, G.;Kar, S.
通讯作者：
Kar, S.
影响因子：
5.5
作者：
Friedman D;Honig LS;Scarmeas N
通讯作者：
Scarmeas N
影响因子：
15.9
作者：
Kong, Qiongman;Chang, Ling-Chu;Lin, Chien-Liang Glenn
通讯作者：
Lin, Chien-Liang Glenn
DOI：
10.1073/pnas.96.6.3228
发表时间：
1999-03-16
影响因子：
11.1
作者：
Hsia, AY;Masliah, E;Mucke, L
通讯作者：
Mucke, L