Congenital myasthenic syndromes: Multiple molecular targets at the neuromuscular junction
Congenital myasthenic syndromes: Multiple molecular targets at the neuromuscular junction
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DOI：
10.1196/annals.1254.016
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Sine, SM
中科院分区：
文献类型：
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作者：
Engel, AG;Ohno, K;Sine, SM
先天性肌无力综合征（CMS）源于突触前、突触和突触后蛋白质的缺陷。突触前CMS与减少乙酰胆碱（ACh）量子的诱发释放或ACh再合成的缺陷有关。乙酰胆碱再合成的缺陷现在已经被追踪到胆碱乙酰转移酶的突变。突触CMS是由乙酰胆碱酯酶终板种类的胶原尾亚基（ColQ）中的突变引起的，所述突变阻止尾亚基与催化亚基缔合或插入到突触基底层中。大多数突触后CMS是由乙酰胆碱受体（AChR）亚基突变引起的，这些突变改变了动力学特性或降低了AChR的表达。动力学突变增加或减少对ACh的突触反应，并分别导致慢通道和快通道综合征。大多数低表达突变存在于AChR e亚基中，并通过胎儿型γ亚基的残留表达而部分补偿。在CMS患者的一个子集中，终板AChR缺陷是由rapsyn突变引起的，rapsyn是一种在突触后膜中浓缩AChR中起关键作用的分子。
Congenital myasthenic syndromes (CMS) stem from defects in presynaptic, synaptic, and postsynaptic proteins. The presynaptic CMS are associated with defects that curtail the evoked release of acetylcholine (ACh) quanta or ACh resynthesis. Defects in ACh resynthesis have now been traced to mutations in choline acetyltransferase. A synaptic CMS is caused by mutations in the collagenic tail subunit (ColQ) of the endplate species of acetylcholinesterase that prevent the tail subunit from associating with catalytic subunits or from becoming inserted into the synaptic basal lamina. Most postsynaptic CMS are caused by mutations in subunits of the acetylcholine receptor (AChR) that alter the kinetic properties or decrease the expression of AChR. The kinetic mutations increase or decrease the synaptic response to ACh and result in slow- and fast-channel syndromes, respectively. Most low-expressor mutations reside in the AChR e subunit and are partially compensated by residual expression of the fetal-type gamma subunit. In a subset of CMS patients, endplate AChR deficiency is caused by mutations in rapsyn, a molecule that plays a critical role in concentrating AChR in the postsynaptic membrane.