{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:32:07Z","timestamp":1787027527259,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01-NS108686"],"award-info":[{"award-number":["R01-NS108686"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01-AG0624069"],"award-info":[{"award-number":["R01-AG0624069"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RF1-AG062135"],"award-info":[{"award-number":["RF1-AG062135"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Oxidative stress in Alzheimer\u2019s disease (AD) is mediated, in part, by the loss of glutathione (GSH). Previous studies show that \u03b3-glutamyl transpeptidase (GGT)-resistant GSH analog, \u03a8-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 \u03a8-GSH can attenuate the disease progression when administered following the onset of AD-like pathology in vivo. Cohorts of APP\/PS1 mice were administered \u03a8-GSH for 2 months starting at 8 month or 12 months of age. We show that \u03a8-GSH treatment reduces indices of oxidative stress in older mice by restoration of enzyme glyoxalase-1 (Glo-1) activity and reduces levels of insoluble A\u03b2. Quantitative neuropathological analyses show that \u03a8-GSH treatment significantly reduces A\u03b2 deposition and brain inflammation in APP\/PS1 mice compared to vehicle-treated mice. More importantly, \u03a8-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 \u03a8-GSH exhibits significant antioxidant activity in aged APP\/PS1 mice and chronic \u03a8-GSH treatment administered after the onset of AD pathology can reverse\/slow further progression of AD-like pathology and neurodegeneration in vivo.<\/jats:p>","DOI":"10.3390\/antiox10111796","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T09:19:21Z","timestamp":1636535961000},"page":"1796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["\u03b3-Glutamyl-Transpeptidase-Resistant Glutathione Analog Attenuates Progression of Alzheimer\u2019s Disease-like Pathology and Neurodegeneration in a Mouse Model"],"prefix":"10.3390","volume":"10","author":[{"given":"Ye In","family":"Christopher Kwon","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xie","sequence":"additional","affiliation":[{"name":"Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haizhou","family":"Zhu","sequence":"additional","affiliation":[{"name":"Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiashu","family":"Xie","sequence":"additional","affiliation":[{"name":"Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keaton","family":"Shinn","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Juckel","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Vince","sequence":"additional","affiliation":[{"name":"Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8733-2029","authenticated-orcid":false,"given":"Swati S.","family":"More","sequence":"additional","affiliation":[{"name":"Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5865-9682","authenticated-orcid":false,"given":"Michael K.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2021). 2021 Alzheimer\u2019s disease facts and figures. 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