The neuromuscular junction (NMJ) is indispensable for survival. This synapse between motoneurons and skeletal muscle fibers allows posture, movement and respiration. Therefore, its dysfunction creates pathologies than can be lethal. The molecular mechanisms of NMJ development and maintenance are the subject of intensive studies. This mini-review focuses on some of the most recent discoveries. An unexpected role for a protein, rapsyn, which has been known for 40 years to aggregate acetylcholine receptors has emerged. A new cell partner at NMJ has been unmasked and is challenging our understanding of the functioning of this synapse. Toxins are now used as new tools to study degeneration/regeneration. The possibility of creating human NMJ in vitro is within reach with major consequences for drug screening. Wnts are secreted neurogenic factors that have been involved in vitro in acetylcholine receptor clustering, but their precise role in vivo remains to be clarified. All these data are raising new and exciting perspectives in the field and are discussed in this Review. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.
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http://dx.doi.org/10.1111/jnc.14028 | DOI Listing |
Pflugers Arch
January 2025
Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, 2/31 Lobachevsky St, Kazan, 420111, RT, Russia.
Many synaptic vesicles undergo exocytosis in motor nerve terminals during neuromuscular communication. Endocytosis then recovers the synaptic vesicle pool and presynaptic membrane area. The kinetics of endocytosis may shape neuromuscular transmission, determining its long-term reliability.
View Article and Find Full Text PDFObjectives: The current gold standard for immunofluorescent (IF) visualization of neuromuscular junctions (NMJs) in muscle utilizes frozen tissue sections with fluorescent conjugated antibodies to demarcate neurons and IF alpha-bungarotoxin (α-BTX) to demarcate motor endplates. Frozen tissue sectioning comes with inherent inescapable limitations, including cryosectioning artifact and limited sample shelf-life. However, a parallel approach to identify NMJs in paraffin-embedded tissue sections has not been previously described.
View Article and Find Full Text PDFMuscle Nerve
January 2025
Division of Plastic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Introduction: Motor recovery following nerve injury is dependent on time required for muscle reinnervation. This process is imperfect, however, and recovery is often incomplete. At the neuromuscular junction (NMJ), macrophage signaling aids muscle reinnervation.
View Article and Find Full Text PDFJ Physiol
January 2025
Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
We previously reported that elevated expression of phospholipid hydroperoxide glutathione peroxidase 4, an enzyme that regulates membrane lipid hydroperoxides, can mitigate sarcopenia in mice. However, it is still unknown whether a pharmacological intervention designed to modulate lipid hydroperoxides might be an effective strategy to reduce sarcopenia in aged mice. Here we asked whether a newly developed compound, CMD-35647 (CMD), can reduce muscle atrophy induced by sciatic nerve transection.
View Article and Find Full Text PDFEur J Neurol
January 2025
Neuromuscular Unit, Neurology Department, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Background: Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy. In this study, we aimed to analyze the genetic spectrum and describe phenotypic features in a large cohort from Türkiye.
Methods: Demographic and clinical findings were recorded.
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