Mitochondrial bioenergetics in ocular fibroblasts of two myasthenia gravis cases

Europa, Tarin A.; Nel, Melissa; Lebeko, Maribanyana; Heckmann, Jeannine M.

doi:10.1016/j.ibneur.2022.04.007

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…Moreover, the overexpression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), a regulator of mitochondrial biogenesis, can correct neuromuscular dysfunction in cachectic skeletal muscle cells [85]. Furthermore, sera from MG patients can alter the bioenergetic metabolism of mitochondria, enhancing oxidative metabolism and glycolysis [86].…”

Section: Pathological Role Of Mitochondria In Mgmentioning

confidence: 99%

Nanodrug Delivery Systems for Myasthenia Gravis: Advances and Perspectives

Huang,

Yan,

Song

et al. 2024

Pharmaceutics

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Myasthenia gravis (MG) is a rare chronic autoimmune disease caused by the production of autoantibodies against the postsynaptic membrane receptors present at the neuromuscular junction. This condition is characterized by fatigue and muscle weakness, including diplopia, ptosis, and systemic impairment. Emerging evidence suggests that in addition to immune dysregulation, the pathogenesis of MG may involve mitochondrial damage and ferroptosis. Mitochondria are the primary site of energy production, and the reactive oxygen species (ROS) generated due to mitochondrial dysfunction can induce ferroptosis. Nanomedicines have been extensively employed to treat various disorders due to their modifiability and good biocompatibility, but their application in MG management has been rather limited. Nevertheless, nanodrug delivery systems that carry immunomodulatory agents, anti-oxidants, or ferroptosis inhibitors could be effective for the treatment of MG. Therefore, this review focuses on various nanoplatforms aimed at attenuating immune dysregulation, restoring mitochondrial function, and inhibiting ferroptosis that could potentially serve as promising agents for targeted MG therapy.

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Section: Pathological Role Of Mitochondria In Mgmentioning

confidence: 99%

Nanodrug Delivery Systems for Myasthenia Gravis: Advances and Perspectives

Huang,

Yan,

Song

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

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Bruton Tyrosine Kinase Inhibition Decreases Inflammation and Differentially Impacts Phagocytosis and Cellular Metabolism in Mouse- and Human-derived Myeloid Cells

Benoit,

Zagrodnik,

Carew

et al. 2024

ImmunoHorizons

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Bruton tyrosine kinase (BTK) is a kinase expressed by various immune cells and is often activated under proinflammatory states. Although the majority of BTK-related research has historically focused on B cells, understanding the role of BTK in non-B cell populations is critical given myeloid cells also express BTK at comparable levels. In this study, we investigated and compared how BTK inhibition in human and murine myeloid cells alters cell phenotype and function. All experiments were performed using two BTK inhibitors (evobrutinib and tolebrutinib) that are currently in late-stage clinical trials for the treatment of multiple sclerosis. Assays were performed to assess the impact of BTK inhibition on cytokine and microRNA expression, phagocytic capacity, and cellular metabolism. In all cells, both evobrutinib and tolebrutinib significantly decreased phosphorylated BTK and LPS-induced cytokine release. BTK inhibition also significantly decreased the oxygen consumption rate and extracellular acidification rate in myeloid cells, and significantly decreased phagocytosis in murine-derived cells, but not human macrophages. To further elucidate the mechanism, we also investigated the expression of microRNAs known to impact the function of myeloid cells. BTK inhibition resulted in an altered microRNA expression profile (i.e., decreased miR-155-5p and increased miR-223-3p), which is consistent with a decreased proinflammatory myeloid cell phenotype. In summary, these results provide further insights into the mechanism of action of BTK inhibitors in the context of immune-related diseases, while also highlighting important species-specific and cell-specific differences that should be considered when interpreting and comparing results between preclinical and human studies.

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Mitochondrial bioenergetics in ocular fibroblasts of two myasthenia gravis cases

Cited by 2 publications

References 26 publications

Nanodrug Delivery Systems for Myasthenia Gravis: Advances and Perspectives

Nanodrug Delivery Systems for Myasthenia Gravis: Advances and Perspectives

Bruton Tyrosine Kinase Inhibition Decreases Inflammation and Differentially Impacts Phagocytosis and Cellular Metabolism in Mouse- and Human-derived Myeloid Cells

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