Autoimmune attack of the neuromuscular junction in myasthenia gravis : nicotinic acetylcholine receptors and other targets
Abstract: The nicotinic acetylcholine receptor (nAChR) family, the archetype member of the pentameric ligand-gated ion channels, is ubiquitously distributed in the central and peripheral nervous systems and its members are the targets for both genetic and acquired forms of neurological disorders. In the central nervous system nAChRs contribute to the pathological mechanisms of neurodegenerative disorders, such as Alzheimer and Parkinson diseases. In the peripheral nerve-muscle synapse, the vertebrate neuromuscular junction, “classical” myasthenia gravis (MG) and other forms of neuromuscular transmission disorders are antibody-mediated autoimmune diseases. In MG, antibodies to the nAChR bind to the postsynaptic receptors and activate the classical complement pathway culminating in the formation of the membrane attack complex, with the subsequent destruction of the postsynaptic apparatus. Divalent nAChR-antibodies also cause internalization and loss of the nAChRs. Loss of receptors by either mechanism results in the muscle weakness and fatigability that typify the clinical manifestations of the disease. Other targets for antibodies, in a minority of patients, include muscle specific kinase (MuSK) and low-density lipoprotein related protein 4 (LRP4). This brief review analyzes the current status of muscle-type nAChR in relation to the pathogenesis of autoimmune diseases affecting the peripheral cholinergic synapse.
| Main Authors: | , |
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| Format: | Artículo biblioteca |
| Language: | eng |
| Published: |
American Chemical Society
2019
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| Subjects: | MIASTENIA GRAVIS, ENFERMEDADES AUTOINMUNES, ANTICUERPOS, RECEPTORES, SISTEMA NERVIOSO, |
| Online Access: | https://repositorio.uca.edu.ar/handle/123456789/9010 |
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| Summary: | Abstract: The nicotinic acetylcholine receptor (nAChR) family, the archetype member of the
pentameric ligand-gated ion channels, is ubiquitously distributed in the central and
peripheral nervous systems and its members are the targets for both genetic and acquired
forms of neurological disorders. In the central nervous system nAChRs contribute to the
pathological mechanisms of neurodegenerative disorders, such as Alzheimer and
Parkinson diseases. In the peripheral nerve-muscle synapse, the vertebrate
neuromuscular junction, “classical” myasthenia gravis (MG) and other forms of
neuromuscular transmission disorders are antibody-mediated autoimmune diseases. In
MG, antibodies to the nAChR bind to the postsynaptic receptors and activate the classical
complement pathway culminating in the formation of the membrane attack complex, with
the subsequent destruction of the postsynaptic apparatus. Divalent nAChR-antibodies also
cause internalization and loss of the nAChRs. Loss of receptors by either mechanism
results in the muscle weakness and fatigability that typify the clinical manifestations of the
disease. Other targets for antibodies, in a minority of patients, include muscle specific
kinase (MuSK) and low-density lipoprotein related protein 4 (LRP4). This brief review
analyzes the current status of muscle-type nAChR in relation to the pathogenesis of
autoimmune diseases affecting the peripheral cholinergic synapse. |
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