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首页> 外文期刊>Epilepsy research >A new paradigm of channelopathy in epilepsy syndromes: intracellular trafficking abnormality of channel molecules.
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A new paradigm of channelopathy in epilepsy syndromes: intracellular trafficking abnormality of channel molecules.

机译：癫痫综合征中通道病的新范例：通道分子的细胞内运输异常。

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Mutations in genes encoding ion channels in brain neurons have been identified in various epilepsy syndromes. In neuronal networks, "gain-of-function" of channels in excitatory neurotransmission could lead to hyper-excitation while "loss-of-function" in inhibitory transmission impairs neuronal inhibitory system, both of which can result in epilepsy. A working hypothesis to view epilepsy as a disorder of channel or "channelopathy" seems rational to explore the pathogenesis of epilepsy. However, the imbalance resulting from channel dysfunction is not sufficient to delineate the pathogenesis of all epilepsy syndromes of which the underlying channel abnormalities have been verified. Mutations identified in epilepsy, mainly in genes encoding subunits of GABA(A) receptors, undermine intracellular trafficking, thus leading to retention of channel molecules in the endoplasmic reticulum (ER). This process may cause ER stress followed by apoptosis, which is a known pathomechanism of certain neurodegenerative disorders. Thus, the pathomechanism of "channel trafficking abnormality" may provide a new paradigm to channelopathy to unsolved questions underlying epilepsy, such as differences between generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy in infancy, which share the causative genetic abnormalities in the same genes and hence are so far considered to be within the spectrum of one disease entity or allelic variants.
机译：在各种癫痫综合症中已经发现了编码大脑神经元离子通道的基因突变。在神经元网络中，兴奋性神经传递中通道的“功能获得”可能会导致过度兴奋，而抑制性传递中的“功能丧失”则会损害神经元抑制系统，这两者都可能导致癫痫。将癫痫病视为通道疾病或“通道病”的有效假设似乎对探索癫痫的发病机理是合理的。然而，由通道功能障碍引起的失衡不足以描述所有潜在的通道异常已被证实的癫痫综合征的发病机理。在癫痫病中发现的突变，主要是在编码GABA（A）受体亚基的基因中，破坏了细胞内运输，从而导致通道分子保留在内质网（ER）中。这个过程可能引起内质网应激，随后是细胞凋亡，这是某些神经退行性疾病的已知机制。因此，“渠道贩运异常”的发病机制可能为解决尚未解决的癫痫病的问题提供通道病的新范例，例如广义癫痫伴高热性癫痫发作和婴儿期严重的肌阵挛性癫痫之间的差异，它们在同一基因中具有共同的致病性遗传异常。因此迄今被认为在一种疾病实体或等位基因变体的范围内。

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