6533b82afe1ef96bd128cb20

RESEARCH PRODUCT

Expression of the Acetylcholine Receptor α-Subunit Gene is Associated with Paraneoplastic Myasthenia Gravis in Mixed Thymoma

Socrates J. TzartosChristiane SchneiderAlexander MarxHans Konrad Müller-hermelinkWilfried NixA. SchultzStefanie GutscheViola HoffackerBerthold SchalkeA. Wilisch

subject

Gene isoformanimal structuresChemistryAlternative splicingmusculoskeletal systemmedicine.diseasemedicine.disease_causeMolecular biologyNeuromuscular junctionMyasthenia gravisAcetylcholine bindingMolecular mimicrymedicine.anatomical_structureNicotinic agonistmedicinetissuesAcetylcholine receptor

description

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies against the acetylcholine receptor (AChR) at the neuromuscular junction [1]. The muscular AChR has been extensively characterized [2], but the etiology of MG is still obscure. Whether the muscular AChR or another (auto)antigen plays a role during the initiation of MG is unknown [3]. The muscular AChR is a pentameric ion channel composed of four different subunits. The α-subunit contains the acetylcholine binding site and the main epitopes recognized by MG autoantibodies [2]. The human muscle AChR α-subunit exists as two isoforms, P3A- and P3A+ [4]. This is a result of alternative splicing of the P3A exon located between exons three and four. The P3A+ isoform does not bind α-bungarotoxin or monoclonal antibodies against the AChR main immunogenic region and is not integrated into functional AChR [5]. The muscular AChR belongs to the family of nicotinic AChRs as do neuronal AChRs. Since muscular and neuronal AChRs share significant molecular homology [6], neuronal AChRs have been considered as candidate autoantigens able to elicit autoimmunity against the muscular AChR by molecular mimicry [7].

yearjournalcountryeditionlanguage
2000-01-01
https://doi.org/10.1007/978-94-011-4060-7_5