Amyotrophic Lateral Sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper motor neurons (UMN) and lower motor neurons (LMN). Disease affects people all over the world and is more prevalent in men. Patients with ALS develop extensive muscle wasting, paralysis and ultimately death, with a median survival of usually fewer than five years after disease onset. ALS may be sporadic (sALS, 90%) or familial (fALS, 10%). The large majority of fALS cases are associated with genetic alterations, which are mainly related to the genes SOD1, TDP-43, FUS, and C9ORF72. In vitro and in vivo models have helped elucidate ALS etiology and pathogenesis, as well as its molecular, cellular, and physiological mechanisms. Many studies in cell cultures and animal models, such as Caenorhabditis elegans, Drosophila melanogaster, zebrafish, rodents, and non-human primates have been performed to clarify the relationship of these genes to ALS disease. However, there are inherent limitations to consider when using experimental models. In this review, we provide an updated overview of the most used in vitro and in vivo studies that have contributed to a better understanding of the different ALS pathogenic mechanisms.

中文翻译：

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肌萎缩侧索硬化的体外和体内模型：更新概述。

肌萎缩侧索硬化症 (ALS) 是一种进行性神经退行性疾病，其特征是上运动神经元 (UMN) 和下运动神经元 (LMN) 的丧失。疾病影响世界各地的人们，在男性中更为普遍。ALS 患者会出现广泛的肌肉萎缩、瘫痪并最终死亡，发病后的中位生存期通常不到 5 年。ALS 可能是散发性（sALS，90%）或家族性（fALS，10%）。绝大多数 fALS 病例与遗传改变有关，主要与基因 SOD1、TDP-43、FUS 和 C9ORF72 相关。体外和体内模型有助于阐明 ALS 的病因和发病机制，以及其分子、细胞和生理机制。许多细胞培养和动物模型研究，例如秀丽隐杆线虫、黑腹果蝇、斑马鱼、已经对啮齿动物和非人类灵长类动物进行了研究，以阐明这些基因与 ALS 疾病的关系。但是，在使用实验模型时需要考虑固有的局限性。在这篇综述中，我们提供了最常用的体外和体内研究的最新概述，这些研究有助于更好地了解不同的 ALS 致病机制。