{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T14:15:44Z","timestamp":1784038544796,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation (NRF) of the Korean government","award":["RS-2026-25470627"],"award-info":[{"award-number":["RS-2026-25470627"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Oxidative stress and redox imbalance are central features of both age-related neurodegenerative disorders and the persistent neurological sequelae of coronavirus disease 2019. Increasing evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupts neuronal redox homeostasis via mitochondrial dysfunction, iron dysregulation, inflammatory signaling, and the depletion of pyridine nucleotide pools. In that context, ferroptosis provides a unifying mechanistic framework linking lipid peroxidation to progressive neuronal injury. This review proposes that neuronal vulnerability might depend not only on the oxidative burden itself but also on the failure of membrane-localized antioxidant defenses. Particular emphasis is placed on the plasma membrane redox system (PMRS), a membrane-associated quinone-reducing network that can support coenzyme Q redox cycling and constrain lipid radical propagation at the plasma membrane. Unlike canonical ferroptosis defense systems that rely predominantly on NADPH, components of the PMRS, particularly cytochrome b5 reductase, can also use NADH, conferring partial metabolic flexibility in conditions of redox stress. We further discuss how SARS-CoV-2-induced NAD+ depletion might progressively destabilize this membrane-proximal defense architecture, potentially lowering the ferroptotic threshold of vulnerable neurons. Finally, we outline therapeutic strategies that might reinforce PMRS-dependent membrane redox control through NRF2 activation, NAD+ restoration, coenzyme Q-centered interventions, and modulation of iron-catalyzed lipid oxidation.<\/jats:p>","DOI":"10.3390\/antiox15050572","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T09:33:17Z","timestamp":1777627997000},"page":"572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Plasma Membrane Redox Failure Links COVID-19 Metabolic Stress to Ferroptotic Neurodegeneration"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1184-1756","authenticated-orcid":false,"given":"Jaewang","family":"Lee","sequence":"first","affiliation":[{"name":"LogSynk Ltd., Seoul 06153, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyosin","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Life Science, Ewha Womans University, Seoul 03760, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0542-166X","authenticated-orcid":false,"given":"Dong-Hoon","family":"Hyun","sequence":"additional","affiliation":[{"name":"Department of Life Science, Ewha Womans University, Seoul 03760, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. 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