Cholesterol in myasthenia gravis

Paz, Mariela L.; Barrantes, Francisco J.

doi:10.1016/j.abb.2021.108788

Cited by 7 publications

(6 citation statements)

References 137 publications

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“…Lipid rafts and cholesterol also play a key role in their clustering and stabilization. 19 The extracellular components of the postsynaptic apparatus and the peripheral membrane proteins, such as rapsyn, MuSK, and the nAChRs, are enriched in lipid microdomains prepared from wild-type myotubes in which cholesterol is fundamental for the functionality of the NMJ. 42,49 As a pleiotropic effect of the statins, isoprenoid intermediates are also directly affected, as statins inhibit L-mevalonic acid synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…The nAChRs, being at the top of junctional sarcolemma folds, are fundamental for membrane excitation. Lipid rafts and cholesterol also play a key role in their clustering and stabilization 19 . The extracellular components of the postsynaptic apparatus and the peripheral membrane proteins, such as rapsyn, MuSK, and the nAChRs, are enriched in lipid microdomains prepared from wild‐type myotubes in which cholesterol is fundamental for the functionality of the NMJ 42,49 …”

Section: Discussionmentioning

confidence: 99%

“…7,8 Neuromuscular complications of statin treatment range from mild to severe myopathies, 1,2,[9][10][11][12][13][14][15][16][17][18] and include myasthenia gravis, an autoimmune disease that directly affects neuromuscular junctions (NMJs). 19 This occurrence is mainly reported in association with rosuvastatin and simvastatin. 2 With the widespread global use of statins, population exposure is increasing [20][21][22] ; effects related to human reproduction also need to be investigated and its safety needs to be clarified.…”

Section: Introductionmentioning

confidence: 99%

“…Neuromuscular complications of statin treatment range from mild to severe myopathies, 1,2,9–18 and include myasthenia gravis, an autoimmune disease that directly affects neuromuscular junctions (NMJs) 19 . This occurrence is mainly reported in association with rosuvastatin and simvastatin 2 …”

Section: Introductionmentioning

confidence: 99%

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Statin exposure during pregnancy promotes neuromuscular junction alterations in postpartum Wistar rats

et al. 2023

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Introduction/Aims The mechanisms that underlie the pathogenesis of statin‐associated muscle symptoms (SAMS) remain unclear. Pregnancy is associated with increased cholesterol levels. Statins may be useful during pregnancy, but their safety is uncertain. Hence, we investigated the postpartum effects of exposure to rosuvastatin and simvastatin during pregnancy in Wistar rats, targeting the neuromuscular structures. Methods Twenty‐one pregnant Wistar rats were divided into three groups: control (C) treated with vehicle (dimethylsulfoxide + dH20), simvastatin (S) 62.5 mg/kg/day, and rosuvastatin (R) 10 mg/kg/day. Gavage was performed daily from the gestational days 8 to 20. At weaning, the postpartum mother tissues were collected and subjected to morphological and morphometric analysis of the soleus muscle, associated neuromuscular junctions (NMJs), and the sciatic nerve; protein quantification; quantification of the cholesterol and creatine kinase in the serum; and intramuscular collagen analysis. Results An increase in morphometric parameters (area, maximum and minimum diameters, Feret diameter, and minimum Feret) was observed in NMJs from the S and R groups in comparison with the C group, and there was also a loss of common NMJ circularity. The number of myofibers with central nuclei was higher in S (17 ± 3.9, P = .0083) and R (18.86 ± 14.42, P = .0498) than in C (6.8 ± 2.6). Discussion Gestational exposure to statins induced postpartum NMJ morphology alterations in soleus muscle, which may be caused by the remodeling of clusters of nicotinic acetylcholine receptors. This may be associated with the development and progression of SAMS observed in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Statin exposure during pregnancy promotes neuromuscular junction alterations in postpartum Wistar rats

et al. 2023

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“…The behavior of mAb35 is thus presumed to resemble that of the pathogenic autoantibodies found in the human disease. In vitro , myasthenia gravis antibodies have been shown to bind divalently to the nAChR, presumably via the two α-subunits of adjacent receptor monomers and thus crosslink receptors (see reviews in ( Paz and Barrantes, 2019 , 2021 )). Using mAb35 as a tool to tag in vitro cell-surface muscle-type nAChRs, we experimentally observed that the translational motion of the receptor macromolecule upon multivalent ligand (antibody) binding ( Mosqueira et al, 2020 ) differed from the diffusion of the receptor labeled with the monovalent non-crosslinking ligand, fluorescent α-bungarotoxin.…”

Section: Fluorescence Microscopy To Study the Nanoscale And Mesoscale...mentioning

confidence: 99%

Fluorescence microscopy imaging of a neurotransmitter receptor and its cell membrane lipid milieu

Barrantes

2022

Front. Mol. Biosci.

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Hampered by the diffraction phenomenon, as expressed in 1873 by Abbe, applications of optical microscopy to image biological structures were for a long time limited to resolutions above the ∼200 nm barrier and restricted to the observation of stained specimens. The introduction of fluorescence was a game changer, and since its inception it became the gold standard technique in biological microscopy. The plasma membrane is a tenuous envelope of 4 nm–10 nm in thickness surrounding the cell. Because of its highly versatile spectroscopic properties and availability of suitable instrumentation, fluorescence techniques epitomize the current approach to study this delicate structure and its molecular constituents. The wide spectral range covered by fluorescence, intimately linked to the availability of appropriate intrinsic and extrinsic probes, provides the ability to dissect membrane constituents at the molecular scale in the spatial domain. In addition, the time resolution capabilities of fluorescence methods provide complementary high precision for studying the behavior of membrane molecules in the time domain. This review illustrates the value of various fluorescence techniques to extract information on the topography and motion of plasma membrane receptors. To this end I resort to a paradigmatic membrane-bound neurotransmitter receptor, the nicotinic acetylcholine receptor (nAChR). The structural and dynamic picture emerging from studies of this prototypic pentameric ligand-gated ion channel can be extrapolated not only to other members of this superfamily of ion channels but to other membrane-bound proteins. I also briefly discuss the various emerging techniques in the field of biomembrane labeling with new organic chemistry strategies oriented to applications in fluorescence nanoscopy, the form of fluorescence microscopy that is expanding the depth and scope of interrogation of membrane-associated phenomena.

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The Management of Hypercholesterolemia in Patients with Neuromuscular Disorder

Loh

Watts

2023

Curr Atheroscler Rep

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Cholesterol in myasthenia gravis

Cited by 7 publications

References 137 publications

Statin exposure during pregnancy promotes neuromuscular junction alterations in postpartum Wistar rats

Statin exposure during pregnancy promotes neuromuscular junction alterations in postpartum Wistar rats

Fluorescence microscopy imaging of a neurotransmitter receptor and its cell membrane lipid milieu

The Management of Hypercholesterolemia in Patients with Neuromuscular Disorder

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