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.

Center of Biosciences Institute of Molecular Physiology and Genetics Slovak Academy of Sciences Bratislava Slovakia

Department of Pathophysiology 3rd Faculty of Medicine Charles University Prague Czech Republic

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic

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Pipeline—QurAlis. 2023. Available from: https://www.quralis.com/pipeline/.

Electrophysiological characterization of sourced human iPSC-derived motor neurons