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.

中文翻译：

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褪黑激素：一种铁死亡抑制剂，对 COVID-19 后加速的大脑老化和神经退行性疾病具有潜在的治疗功效


史无前例的 COVID-19 大流行在短时间内席卷了数百万人的生命，但它的威胁仍然以新冠后综合症的形式持续存在于幸存者中。患有认知障碍的 COVID-19 幸存者数量呈指数级增长，有令人信服的证据表明其加速衰老和神经退行性疾病的轨迹。这种尚未揭示的病理学的新颖性和神秘性需要进行广泛的研究，以寻求分子基础和潜在治疗靶点的答案。铁死亡是一种铁依赖性细胞死亡，是 COVID-19 后衰老和神经退行性疾病讨论中强烈提出的潜在机制。 COVID-19 会引发神经炎症、铁失调、活性氧 (ROS) 积累、抗氧化系统抑制、肾素-血管紧张素系统 (RAS) 破坏和时钟基因改变。这些事件为铁死亡铺平了道路，铁死亡在 COVID-19、过早衰老和神经退行性疾病中表现出其特征。在寻找治疗方法的过程中，褪黑激素因其多次报道的安全性和耐受性而成为一种有前途的铁死亡抑制剂。根据多项研究，褪黑激素已被证明可以有效减轻某些 COVID-19 症状的严重程度，从而验证了其作为抗病毒化合物的声誉。褪黑激素具有充分记录的抗衰老特性和对抗神经退行性相关病理的作用。褪黑激素可以阻止铁死亡的主要事件，因为它是一种有效的抗炎剂、铁螯合剂、抗氧化剂、血管紧张素 II 拮抗剂和时钟基因调节剂。因此，我们建议铁死亡是 COVID-19 后衰老和神经退行性疾病轨迹背后的罪魁祸首，而褪黑激素（一种非常合适的铁死亡抑制剂）可以作为一种潜在的治疗方法。