Schattling Benjamin, Eggert Britta, Friese Manuel A
Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Falkenried 94, D-20251 Hamburg, Germany.
Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Falkenried 94, D-20251 Hamburg, Germany.
Exp Neurol. 2014 Dec;262 Pt A:28-36. doi: 10.1016/j.expneurol.2013.12.006. Epub 2014 Mar 20.
Multiple sclerosis (MS), the most frequent inflammatory disease of the central nervous system (CNS), affects about two and a half million individuals worldwide and causes major burdens to the patients, which develop the disease usually at the age of 20 to 40. MS is likely referable to a breakdown of immune cell tolerance to CNS self-antigens resulting in focal immune cell infiltration, activation of microglia and astrocytes, demyelination and axonal and neuronal loss. Here we discuss how altered expression patterns and dysregulated functions of ion channels contribute on a molecular level to nearly all pathophysiological steps of the disease. In particular the detrimental redistribution of ion channels along axons, as well as neuronal excitotoxicity with regard to imbalanced glutamate homeostasis during chronic CNS inflammation will be discussed in detail. Together, we describe which ion channels in the immune and nervous system commend as attractive future drugable targets in MS treatment.
多发性硬化症（MS）是中枢神经系统（CNS）最常见的炎症性疾病，全球约有250万人受其影响，给患者带来了沉重负担，患者通常在20至40岁时发病。MS可能是由于免疫细胞对CNS自身抗原的耐受性破坏，导致局部免疫细胞浸润、小胶质细胞和星形胶质细胞激活、脱髓鞘以及轴突和神经元丢失。在这里，我们讨论离子通道表达模式的改变和功能失调如何在分子水平上对该疾病几乎所有的病理生理步骤产生影响。特别是将详细讨论离子通道沿轴突的有害重新分布，以及慢性CNS炎症期间谷氨酸稳态失衡导致的神经元兴奋性毒性。我们共同描述了免疫和神经系统中的哪些离子通道有望成为MS治疗中未来有吸引力的可药物靶向目标。
