Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration

DOI record: { "DOI": "10.1186/s13024-024-00728-6", "ISSN": [ "1750-1326" ], "URL": "http://dx.doi.org/10.1186/s13024-024-00728-6", "abstract": "<jats:title>Abstract</jats:title><jats:p>The unprecedented pandemic of COVID-19 swept millions of lives in a short period, yet its menace continues among its survivors in the form of post-COVID syndrome. An exponentially growing number of COVID-19 survivors suffer from cognitive impairment, with compelling evidence of a trajectory of accelerated aging and neurodegeneration. The novel and enigmatic nature of this yet-to-unfold pathology demands extensive research seeking answers for both the molecular underpinnings and potential therapeutic targets. Ferroptosis, an iron-dependent cell death, is a strongly proposed underlying mechanism in post-COVID-19 aging and neurodegeneration discourse. COVID-19 incites neuroinflammation, iron dysregulation, reactive oxygen species (ROS) accumulation, antioxidant system repression, renin-angiotensin system (RAS) disruption, and clock gene alteration. These events pave the way for ferroptosis, which shows its signature in COVID-19, premature aging, and neurodegenerative disorders. In the search for a treatment, melatonin shines as a promising ferroptosis inhibitor with its repeatedly reported safety and tolerability. According to various studies, melatonin has proven efficacy in attenuating the severity of certain COVID-19 manifestations, validating its reputation as an anti-viral compound. Melatonin has well-documented anti-aging properties and combating neurodegenerative-related pathologies. Melatonin can block the leading events of ferroptosis since it is an efficient anti-inflammatory, iron chelator, antioxidant, angiotensin II antagonist, and clock gene regulator. Therefore, we propose ferroptosis as the culprit behind the post-COVID-19 trajectory of aging and neurodegeneration and melatonin, a well-fitting ferroptosis inhibitor, as a potential treatment.</jats:p>", "alternative-id": [ "728" ], "article-number": "36", "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "7 February 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 2, "value": "15 April 2024" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 3, "value": "19 April 2024" }, { "group": { "label": "Declarations", "name": "EthicsHeading" }, "name": "Ethics", "order": 1 }, { "group": { "label": "Consent for publication", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "value": "This manuscript does not contain data from any individual person so the consent for publication is not applicable." }, { "group": { "label": "Ethics approval and consent to participate", "name": "EthicsHeading" }, "name": "Ethics", "order": 3, "value": "Not applicable. Ethics approval and consent are not indicated due to the review nature of this paper." }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 4, "value": "The authors declare that they have no competing interests." } ], "author": [ { "affiliation": [], "family": "Yehia", "given": "Asmaa", "sequence": "first" }, { "ORCID": "http://orcid.org/0000-0002-0652-0862", "affiliation": [], "authenticated-orcid": false, "family": "Abulseoud", "given": "Osama A.", "sequence": "additional" } ], "container-title": "Molecular Neurodegeneration", "container-title-short": "Mol Neurodegeneration", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2024, 4, 19 ] ], "date-time": "2024-04-19T13:02:03Z", "timestamp": 1713531723000 }, "deposited": { "date-parts": [ [ 2024, 4, 19 ] ], "date-time": "2024-04-19T14:03:31Z", "timestamp": 1713535411000 }, "indexed": { "date-parts": [ [ 2024, 4, 19 ] ], "date-time": "2024-04-19T14:40:50Z", "timestamp": 1713537650210 }, "is-referenced-by-count": 0, "issue": "1", "issued": { "date-parts": [ [ 2024, 4, 19 ] ] }, "journal-issue": { "issue": "1", "published-online": { "date-parts": [ [ 2024, 12 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 4, 19 ] ], "date-time": "2024-04-19T00:00:00Z", "timestamp": 1713484800000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 4, 19 ] ], "date-time": "2024-04-19T00:00:00Z", "timestamp": 1713484800000 } } ], "link": [ { "URL": "https://link.springer.com/content/pdf/10.1186/s13024-024-00728-6.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/article/10.1186/s13024-024-00728-6/fulltext.html", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://link.springer.com/content/pdf/10.1186/s13024-024-00728-6.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "prefix": "10.1186", "published": { "date-parts": [ [ 2024, 4, 19 ] ] }, "published-online": { "date-parts": [ [ 2024, 4, 19 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.21203/rs.3.rs-1313103/v1", "author": "M Marzouk", "doi-asserted-by": "publisher", "key": "728_CR1", "unstructured": "Marzouk M, et al. 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