{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T08:40:53Z","timestamp":1771231253749,"version":"3.50.1"},"reference-count":122,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T00:00:00Z","timestamp":1653782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH)","award":["AG042178"],"award-info":[{"award-number":["AG042178"]}]},{"name":"National Institutes of Health (NIH)","award":["AG047812"],"award-info":[{"award-number":["AG047812"]}]},{"name":"National Institutes of Health (NIH)","award":["NS105473"],"award-info":[{"award-number":["NS105473"]}]},{"name":"National Institutes of Health (NIH)","award":["AG060767"],"award-info":[{"award-number":["AG060767"]}]},{"name":"National Institutes of Health (NIH)","award":["AG069333"],"award-info":[{"award-number":["AG069333"]}]},{"name":"National Institutes of Health (NIH)","award":["AG066347"],"award-info":[{"award-number":["AG066347"]}]},{"name":"National Institutes of Health (NIH)","award":["R41 AG060836"],"award-info":[{"award-number":["R41 AG060836"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder and is the most common cause of dementia in older people. AD is associated with the loss of synapses, oxidative stress, mitochondrial structural and functional abnormalities, microRNA deregulation, inflammatory responses, neuronal loss, accumulation of amyloid-beta (A\u03b2) and phosphorylated tau (p-tau). AD occurs in two forms: early onset, familial AD and late-onset, sporadic AD. Causal factors are still unknown for a vast majority of AD patients. Genetic polymorphisms are proposed to contribute to late-onset AD via age-dependent increases in oxidative stress and mitochondrial abnormalities. Recent research from our lab revealed that reduced levels of Rlip76 induce oxidative stress, mitochondrial dysfunction and synaptic damage, leading to molecular and behavioral phenotypes resembling late-onset AD. Rlip76 is a multifunctional 76 kDa protein encoded by the RALBP1 gene, located on chromosome 18. Rlip is a stress-protective ATPase of the mercapturic acid pathway that couples clathrin-dependent endocytosis with the efflux of glutathione\u2013electrophile conjugates. Rlip is evolutionarily highly conserved across species and is ubiquitously expressed in all tissues, including AD-affected brain regions, the cerebral cortex and hippocampus, where highly active neuronal metabolisms render the cells highly susceptible to intracellular oxidative damage. In the current article, we summarize molecular and cellular features of Rlip and how depleted Rlip may exacerbate oxidative stress, mitochondrial dysfunction and synaptic damage in AD. We also discuss the possible role of Rlip in aspects of learning and memory via axonal growth, dendritic remodeling, and receptor regulation. We conclude with a discussion of the potential for the contribution of genetic polymorphisms in Rlip to AD progression and the potential for Rlip-based therapies.<\/jats:p>","DOI":"10.3390\/ijms23116098","type":"journal-article","created":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T08:50:51Z","timestamp":1653814251000},"page":"6098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer\u2019s Disease?"],"prefix":"10.3390","volume":"23","author":[{"given":"Ashly","family":"Hindle","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4361-4558","authenticated-orcid":false,"given":"Sharda P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4678-6443","authenticated-orcid":false,"given":"Jangampalli Adi","family":"Pradeepkiran","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chhanda","family":"Bose","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-3415","authenticated-orcid":false,"given":"Murali","family":"Vijayan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2102-7459","authenticated-orcid":false,"given":"Sudhir","family":"Kshirsagar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha A.","family":"Sawant","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9560-9948","authenticated-orcid":false,"given":"P. Hemachandra","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Neuroscience & Pharmacology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Neurology, Departments of School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Public Health Department of Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"},{"name":"Department of Speech, Language and Hearing Sciences, School Health Professions, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/ijc.11260","article-title":"Transport of glutathione conjugates and chemotherapeutic drugs by RLIP76 (RALBP1): A novel link between G-protein and tyrosine kinase signaling and drug resistance","volume":"106","author":"Awasthi","year":"2003","journal-title":"Int. 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