Amyotrophic lateral sclerosis (ALS) stands as the most prevalent and severe form of motor neuron disease, affecting an estimated 2 in 100,000 individuals worldwide. It is characterized by the progressive loss of cortical, brainstem, and spinal motor neurons, ultimately resulting in muscle weakness and death. Although the etiology of ALS remains poorly understood in most cases, the remodelling of ion channels and alteration in neuronal excitability represent a hallmark of the disease, manifesting not only during the symptomatic period but also in the early pre-symptomatic stages. In this review, we delve into these alterations observed in ALS patients and preclinical disease models, and explore their consequences on neuronal activities. Furthermore, we discuss the potential of ion channels as therapeutic targets in the context of ALS.

中文翻译：

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肌萎缩侧索硬化症离子通道的病理生理学


肌萎缩侧索硬化症 (ALS) 是运动神经元疾病中最普遍、最严重的一种，估计全世界每 10 万人中就有 2 人受到影响。其特征是皮质、脑干和脊髓运动神经元逐渐丧失，最终导致肌肉无力和死亡。尽管在大多数情况下，ALS 的病因仍知之甚少，但离子通道的重塑和神经元兴奋性的改变是该疾病的标志，不仅表现在症状期，而且表现在症状前的早期阶段。在这篇综述中，我们深入研究了 ALS 患者和临床前疾病模型中观察到的这些变化，并探讨了它们对神经元活动的影响。此外，我们还讨论了离子通道作为 ALS 治疗靶点的潜力。