重症肌无力
突触后电位
神经肌肉接头
乙酰胆碱受体
神经肌肉传递
阿格林
乙酰胆碱
细胞生物学
药理学
化学
神经科学
突触
生物
医学
内分泌学
受体
内科学
作者
Nazanin Ghazanfari,Sofie Trajanovska,Marco Morsch,Simon Liang,Stephen W. Reddel,William D. Phillips
摘要
Abstract While the majority of myasthenia gravis patients express antibodies targeting the acetylcholine receptor, the second most common cohort instead displays autoantibodies against muscle‐specific kinase (MuSK). MuSK is a transmembrane tyrosine kinase found in the postsynaptic membrane of the neuromuscular junction. During development, MuSK serves as a signaling hub, coordinating the alignment of the pre‐ and postsynaptic components of the synapse. Adult mice that received repeated daily injections of IgG from anti‐MuSK + myasthenia gravis patients developed muscle weakness, associated with neuromuscular transmission failure. MuSK autoantibodies are predominantly of the IgG4 type. They suppress the kinase activity of MuSK and the phosphorylation of target proteins in the postsynaptic membrane. Loss of postsynaptic acetylcholine receptors is the primary cause of neuromuscular transmission failure. MuSK autoantibodies also disrupt the capacity of the motor nerve terminal to adaptively increase acetylcholine release in response to the reduced postsynaptic responsiveness to acetylcholine. The passive IgG transfer model of MuSK myasthenia gravis has been used to test candidate treatments. Pyridostigmine, a first‐line cholinesterase inhibitor drug, exacerbated the disease process, while 3,4‐diaminopyridine and albuterol were found to be beneficial in this mouse model.
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