γ-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer’s Disease-like Pathology and Neurodegeneration in a Mouse Model

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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ye In Christopher Kwon, Wei Xie, Haizhou Zhu, Jiashu Xie, Keaton Shinn, Nicholas Juckel, Robert Vince, Swati S. More, Michael K. Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	glyoxalase 1 oxidative stress Alzheimer’s disease progressive neurodegeneration neuroinflammation advanced glycation end products (AGEs) Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/2cdccac0ab3f4519869f07119d79c7b7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2cdccac0ab3f4519869f07119d79c7b7
record_format	dspace
spelling	oai:doaj.org-article:2cdccac0ab3f4519869f07119d79c7b72021-11-25T16:28:44Zγ-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer’s Disease-like Pathology and Neurodegeneration in a Mouse Model10.3390/antiox101117962076-3921https://doaj.org/article/2cdccac0ab3f4519869f07119d79c7b72021-11-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1796https://doaj.org/toc/2076-3921Oxidative 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.Ye In Christopher KwonWei XieHaizhou ZhuJiashu XieKeaton ShinnNicholas JuckelRobert VinceSwati S. MoreMichael K. LeeMDPI AGarticleglyoxalase 1oxidative stressAlzheimer’s diseaseprogressive neurodegenerationneuroinflammationadvanced glycation end products (AGEs)Therapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1796, p 1796 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glyoxalase 1 oxidative stress Alzheimer’s disease progressive neurodegeneration neuroinflammation advanced glycation end products (AGEs) Therapeutics. Pharmacology RM1-950
spellingShingle	glyoxalase 1 oxidative stress Alzheimer’s disease progressive neurodegeneration neuroinflammation advanced glycation end products (AGEs) Therapeutics. Pharmacology RM1-950 Ye In Christopher Kwon Wei Xie Haizhou Zhu Jiashu Xie Keaton Shinn Nicholas Juckel Robert Vince Swati S. More Michael K. Lee γ-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer’s Disease-like Pathology and Neurodegeneration in a Mouse Model
description	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.
format	article
author	Ye In Christopher Kwon Wei Xie Haizhou Zhu Jiashu Xie Keaton Shinn Nicholas Juckel Robert Vince Swati S. More Michael K. Lee
author_facet	Ye In Christopher Kwon Wei Xie Haizhou Zhu Jiashu Xie Keaton Shinn Nicholas Juckel Robert Vince Swati S. More Michael K. Lee
author_sort	Ye In Christopher Kwon
title	γ-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer’s Disease-like Pathology and Neurodegeneration in a Mouse Model
title_short	γ-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer’s Disease-like Pathology and Neurodegeneration in a Mouse Model
title_full	γ-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer’s Disease-like Pathology and Neurodegeneration in a Mouse Model
title_fullStr	γ-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer’s Disease-like Pathology and Neurodegeneration in a Mouse Model
title_full_unstemmed	γ-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer’s Disease-like Pathology and Neurodegeneration in a Mouse Model
title_sort	γ-glutamyl-transpeptidase-resistant glutathione analog attenuates progression of alzheimer’s disease-like pathology and neurodegeneration in a mouse model
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2cdccac0ab3f4519869f07119d79c7b7
work_keys_str_mv	AT yeinchristopherkwon gglutamyltranspeptidaseresistantglutathioneanalogattenuatesprogressionofalzheimersdiseaselikepathologyandneurodegenerationinamousemodel AT weixie gglutamyltranspeptidaseresistantglutathioneanalogattenuatesprogressionofalzheimersdiseaselikepathologyandneurodegenerationinamousemodel AT haizhouzhu gglutamyltranspeptidaseresistantglutathioneanalogattenuatesprogressionofalzheimersdiseaselikepathologyandneurodegenerationinamousemodel AT jiashuxie gglutamyltranspeptidaseresistantglutathioneanalogattenuatesprogressionofalzheimersdiseaselikepathologyandneurodegenerationinamousemodel AT keatonshinn gglutamyltranspeptidaseresistantglutathioneanalogattenuatesprogressionofalzheimersdiseaselikepathologyandneurodegenerationinamousemodel AT nicholasjuckel gglutamyltranspeptidaseresistantglutathioneanalogattenuatesprogressionofalzheimersdiseaselikepathologyandneurodegenerationinamousemodel AT robertvince gglutamyltranspeptidaseresistantglutathioneanalogattenuatesprogressionofalzheimersdiseaselikepathologyandneurodegenerationinamousemodel AT swatismore gglutamyltranspeptidaseresistantglutathioneanalogattenuatesprogressionofalzheimersdiseaselikepathologyandneurodegenerationinamousemodel AT michaelklee gglutamyltranspeptidaseresistantglutathioneanalogattenuatesprogressionofalzheimersdiseaselikepathologyandneurodegenerationinamousemodel
_version_	1718413126591840256

γ-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer’s Disease-like Pathology and Neurodegeneration in a Mouse Model

Ejemplares similares