Low‐Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients
IntroductionLong 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 channel...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1582967/full |
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| author | Etianne Martini Sasso Etianne Martini Sasso Etianne Martini Sasso Natalie Eaton-Fitch Natalie Eaton-Fitch Peter Smith Peter Smith Katsuhiko Muraki Katsuhiko Muraki Sonya Marshall-Gradisnik Sonya Marshall-Gradisnik |
| author_facet | Etianne Martini Sasso Etianne Martini Sasso Etianne Martini Sasso Natalie Eaton-Fitch Natalie Eaton-Fitch Peter Smith Peter Smith Katsuhiko Muraki Katsuhiko Muraki Sonya Marshall-Gradisnik Sonya Marshall-Gradisnik |
| author_sort | Etianne Martini Sasso |
| collection | DOAJ |
| description | IntroductionLong 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.MethodsNK 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.ResultsThe 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).DiscussionOverall, 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. |
| format | Article |
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| institution | Kabale University |
| issn | 2296-889X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-e5210a8643294d7885035975c1dd09692025-08-20T03:54:01ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-05-011210.3389/fmolb.2025.15829671582967Low‐Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patientsEtianne Martini Sasso0Etianne Martini Sasso1Etianne Martini Sasso2Natalie Eaton-Fitch3Natalie Eaton-Fitch4Peter Smith5Peter Smith6Katsuhiko Muraki7Katsuhiko Muraki8Sonya Marshall-Gradisnik9Sonya Marshall-Gradisnik10The National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, AustraliaConsortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, AustraliaSchool of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD, AustraliaThe National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, AustraliaConsortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, AustraliaConsortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, AustraliaQueensland Allergy Services, Gold Coast, AustraliaConsortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, AustraliaLaboratory of Cellular Pharmacology, School of Pharmacy, Aichi-Gakuin University, Nagoya, JapanThe National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, AustraliaConsortium Health International for Myalgic Encephalomyelitis, National Centre for Neuroimmunology and Emerging Diseases, Griffith University, Gold Coast, QLD, AustraliaIntroductionLong 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.MethodsNK 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.ResultsThe 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).DiscussionOverall, 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.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1582967/fullcalciumTRP ion channelsTRPM3long COVIDlow-dose naltrexoneTransient Receptor Potential Melastatin 3 |
| spellingShingle | Etianne Martini Sasso Etianne Martini Sasso Etianne Martini Sasso Natalie Eaton-Fitch Natalie Eaton-Fitch Peter Smith Peter Smith Katsuhiko Muraki Katsuhiko Muraki Sonya Marshall-Gradisnik Sonya Marshall-Gradisnik Low‐Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients Frontiers in Molecular Biosciences calcium TRP ion channels TRPM3 long COVID low-dose naltrexone Transient Receptor Potential Melastatin 3 |
| title | Low‐Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients |
| title_full | Low‐Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients |
| title_fullStr | Low‐Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients |
| title_full_unstemmed | Low‐Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients |
| title_short | Low‐Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients |
| title_sort | low dose naltrexone restored trpm3 ion channel function in natural killer cells from long covid patients |
| topic | calcium TRP ion channels TRPM3 long COVID low-dose naltrexone Transient Receptor Potential Melastatin 3 |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1582967/full |
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