| First Author | Christopher Kwon YI | Year | 2021 |
| Journal | Antioxidants (Basel) | Volume | 10 |
| Issue | 11 | PubMed ID | 34829667 |
| Mgi Jnum | J:351775 | Mgi Id | MGI:7664277 |
| Doi | 10.3390/antiox10111796 | Citation | Christopher Kwon YI, et al. (2021) gamma-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer's Disease-like Pathology and Neurodegeneration in a Mouse Model. Antioxidants (Basel) 10(11) |
| abstractText | Oxidative stress in Alzheimer's disease (AD) is mediated, in part, by the loss of glutathione (GSH). Previous studies show that gamma-glutamyl transpeptidase (GGT)-resistant GSH analog, Psi-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 Psi-GSH can attenuate the disease progression when administered following the onset of AD-like pathology in vivo. Cohorts of APP/PS1 mice were administered Psi-GSH for 2 months starting at 8 month or 12 months of age. We show that Psi-GSH treatment reduces indices of oxidative stress in older mice by restoration of enzyme glyoxalase-1 (Glo-1) activity and reduces levels of insoluble Abeta. Quantitative neuropathological analyses show that Psi-GSH treatment significantly reduces Abeta deposition and brain inflammation in APP/PS1 mice compared to vehicle-treated mice. More importantly, Psi-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 Psi-GSH exhibits significant antioxidant activity in aged APP/PS1 mice and chronic Psi-GSH treatment administered after the onset of AD pathology can reverse/slow further progression of AD-like pathology and neurodegeneration in vivo. |
