γ-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer's Disease-like Pathology and Neurodegeneration in a Mouse Model.
γ-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer's Disease-like Pathology and Neurodegeneration in a Mouse Model.
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DOI：
10.3390/antiox10111796
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发表时间：
2021-11-10
期刊：
影响因子：
--
通讯作者：
Lee MK
中科院分区：
文献类型：
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作者：
Christopher Kwon YI;Xie W;Zhu H;Xie J;Shinn K;Juckel N;Vince R;More SS;Lee MK
Oxidative stress in Alzheimer’s disease (AD) is mediated, in part, by the loss of glutathione (GSH). Previous studies show that γ-glutamyl transpeptidase (GGT)-resistant GSH analog, Ψ-GSH, improves brain GSH levels, reduces oxidative stress markers in brains of APP/PS1 transgenic mice, a mouse model of AD, and attenuates early memory deficits in the APP/PS1 model. Herein, we examined whether Ψ-GSH can attenuate the disease progression when administered following the onset of AD-like pathology in vivo. Cohorts of APP/PS1 mice were administered Ψ-GSH for 2 months starting at 8 month or 12 months of age. We show that Ψ-GSH treatment reduces indices of oxidative stress in older mice by restoration of enzyme glyoxalase-1 (Glo-1) activity and reduces levels of insoluble Aβ. Quantitative neuropathological analyses show that Ψ-GSH treatment significantly reduces Aβ deposition and brain inflammation in APP/PS1 mice compared to vehicle-treated mice. More importantly, Ψ-GSH treatment attenuated the progressive loss of cortical TH+ afferents and the loss of TH+ neurons in the locus coeruleus (LC). Collectively, the results show that Ψ-GSH exhibits significant antioxidant activity in aged APP/PS1 mice and chronic Ψ-GSH treatment administered after the onset of AD pathology can reverse/slow further progression of AD-like pathology and neurodegeneration in vivo.
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影响因子：
--
作者：
Feng Y;Wang X
通讯作者：
Wang X
影响因子：
5
作者：
More, Swati S.;Vartak, Ashish P.;Vince, Robert
通讯作者：
Vince, Robert
影响因子：
5.3
作者：
Liu, Ying;Yoo, Mi-Jeong;Lee, Michael K.
通讯作者：
Lee, Michael K.
DOI：
10.1186/alzrt269
发表时间：
2014
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Cummings JL;Morstorf T;Zhong K
通讯作者：
Zhong K
影响因子：
14
作者：
通讯作者：
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