1. Figure 1 Neuromuscular junction in myasthenia gravis (MG)
Figure 1 | Neuromuscular junction in myasthenia gravis (MG). a | Normal function of neuromuscular junction, with major components implicated in MG shown. Action potential at the presynaptic nerve terminal causes opening of voltage-dependent Ca2+ channels, triggering release of acetylcholine and agrin into the synaptic cleft. Acetylcholine binds to acetylcholine receptors (AChRs), which promote sodium channel opening, which in turn triggers muscle contraction. Agrin binds to the complex formed by low-density lipoprotein receptor-related protein 4 (LRP4) and muscle-specific kinase (MuSK), causing acetylcholine receptor (AChR) clustering, which is required for maintenance of the postsynaptic structures of the neuromuscular junction. b | Major pathogenic mechanisms of the AChR antibodies in MG include complement activation at the neuromuscular junction, which causes formation of membrane attack complexes (MACs) on the muscle membrane and destruction of the typical folds in the sarcolemma (1); antigenic modulation that results in internalization and degradation of surface AChRs (2); and binding of AChR antibodies at the AChR ligand binding site (3), which could directly block acetylcholine binding and, consequently, channel opening. Anti-MuSK and anti-LRP4 antibodies have been shown to block the intermolecular interactions of MuSK or LRP4 respectively, and could thus inhibit the normal mechanisms for maintenance of the organization of the neuromuscular junction (4). Antibodies with known pathogenic involvement in MG are shown in red. c | MG treatment can restore function of the neuromuscular junction by increasing the levels of available acetylcholine (acetylcholinesterase inhibitors; green), which improves signal transduction, or by reducing the concentration of autoantibodies (immunosuppressive drugs, plasma exchange/immunoadsorption, B-cell-targeting therapies; red), which alleviates the pathogenic mechanisms described in (b). KV1.4, voltage-gated potassium channel 1.4; RyR, ryanodine receptor.
Gilhus, N. E. et al. (2016) Myasthenia gravis — autoantibody characteristics and their implications for therapy
Nat. Rev. Neurol. doi: /nrneurol