Low-Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-05-19 eCollection Date: 2025-01-01 DOI:10.3389/fmolb.2025.1582967

Etianne Martini Sasso, Natalie Eaton-Fitch, Peter Smith, Katsuhiko Muraki, Sonya Marshall-Gradisnik

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引用次数: 0

Abstract

Introduction: Long COVID is a multisystemic condition that includes neurocognitive, immunological, gastrointestinal, and cardiovascular manifestations, independent of the severity or duration of the acute SARS-CoV-2 infection. Dysfunctional Transient Receptor Potential Melastatin 3 (TRPM3) ion channels are associated with the pathophysiology of long COVID due to reduced calcium (Ca²⁺) influx, negatively impacting cellular processes in diverse systems. Accumulating evidence suggests the potential therapeutic benefits of low-dose naltrexone (LDN) for people suffering from long COVID. Our study aimed to investigate the efficacy of LDN in restoring TRPM3 ion channel function in natural killer (NK) cells from long COVID patients.

Methods: NK cells were isolated from nine individuals with long COVID, nine healthy controls, and nine individuals with long COVID who were administered LDN (3-4.5 mg/day). Electrophysiological experiments were conducted to assess TRPM3 ion channel functions modulated by pregnenolone sulfate (PregS) and ononetin.

Results: The findings from this current research are the first to demonstrate that long COVID patients treated with LDN have restored TRPM3 ion channel function and validate previous reports of TRPM3 ion channel dysfunction in NK cells from individuals with long COVID not on treatment. There was no significant difference in TRPM3 currents between long COVID patients treated with LDN and healthy controls (HC), in either PregS-induced current amplitude (p > 0.9999) or resistance to ononetin (p > 0.9999).

Discussion: Overall, our findings support LDN as a potentially beneficial treatment for long COVID patients by restoring TRPM3 ion channel function and reestablishing adequate Ca²⁺ influx necessary for homeostatic cellular processes.

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低剂量纳曲酮恢复长冠患者自然杀伤细胞TRPM3离子通道功能。

长冠肺炎是一种多系统疾病，包括神经认知、免疫、胃肠道和心血管表现，与急性SARS-CoV-2感染的严重程度或持续时间无关。由于钙（Ca2+）内流减少，短暂受体电位美拉他汀3 （TRPM3）离子通道功能失调与长冠状病毒的病理生理有关，对多种系统的细胞过程产生负面影响。越来越多的证据表明，低剂量纳曲酮（LDN）对长期感染COVID的人有潜在的治疗益处。本研究旨在探讨LDN在恢复长COVID患者自然杀伤（NK）细胞TRPM3离子通道功能中的作用。方法：分别从9例长冠状病毒感染者、9例健康对照和9例长冠状病毒感染者（LDN (3 ~ 4.5 mg/d)）中分离NK细胞。采用电生理实验研究孕烯醇酮硫酸盐（PregS）和莪术素对TRPM3离子通道的调节作用。结果：目前的研究结果首次证明，接受LDN治疗的长冠状病毒患者恢复了TRPM3离子通道功能，并验证了先前报道的未接受治疗的长冠状病毒患者NK细胞中TRPM3离子通道功能障碍。LDN治疗的长冠患者与健康对照（HC）之间的TRPM3电流在妊娠诱导电流幅值（p > 0.9999）或对ononetin的抗性（p > 0.9999）方面均无显著差异。讨论：总体而言，我们的研究结果支持LDN通过恢复TRPM3离子通道功能和重建稳态细胞过程所需的足够的Ca2+内流，作为长期COVID患者的潜在有益治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.