Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive incurable neurodegenerative disease, which is characterized by selective death of the motoneurons of the spinal cord and brain. Currently, ALS is considered as a disease with a wide range of etiological causes, which trigger the cellular and molecular mechanisms leading to the development of similar clinical symptoms associated with degeneration of motoneurons. At the same time, there is no single hypothesis combining various pathogenetic mechanisms, which makes it difficult to develop an effective neuroprotective therapy. This review is devoted to the analysis of the early pathogenetic mechanisms of ALS and their possible role in the initiation of disease on the basis of the published data and our own research. The data on participation of various elements of the motoneuron–skeletal muscle system and membrane disorders in the initiation and development of ALS in humans and in animal models are presented. The analysis of scientific results of the last decades allows us to conclude that a key role in the initiation of pathogenetic mechanisms of ALS is played by dysfunction/destruction of neuromuscular synapses, distal axonopathy, and changes in skeletal muscle metabolism; the methods for correction of these disorders are promising for the development of therapeutic strategies in ALS.

中文翻译：

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肌萎缩性侧索硬化症的早期功能障碍：发病机理和疾病发作中的作用。

摘要

肌萎缩性侧索硬化症（ALS）是一种进行性无法治愈的神经退行性疾病，其特征是脊髓和大脑的运动神经元选择性死亡。当前，ALS被认为是具有多种病因的疾病，其触发细胞和分子机制，导致与运动神经元变性相关的相似临床症状的发展。同时，没有单一的假说结合了多种致病机制，这使得开发有效的神经保护疗法变得困难。这篇综述致力于根据已发表的数据和我们自己的研究来分析ALS的早期致病机制及其在疾病引发中的可能作用。本文介绍了有关人和动物模型中ALS的启动和发育过程中运动神经元-骨骼肌系统各种成分和膜异常的参与情况。对过去几十年的科学结果进行的分析使我们得出结论，在ALS发病机制的启动中，关键作用是神经肌肉突触功能障碍/破坏，远端轴突病变和骨骼肌代谢的改变。纠正这些疾病的方法对于发展ALS的治疗策略很有希望。对过去几十年的科学结果进行的分析使我们得出结论，在ALS发病机制的启动中，关键作用是神经肌肉突触功能障碍/破坏，远端轴突病变和骨骼肌代谢的改变。纠正这些疾病的方法对于发展ALS的治疗策略很有希望。对过去几十年的科学结果进行的分析使我们得出结论，在ALS发病机制的启动中，关键作用是神经肌肉突触功能障碍/破坏，远端轴突病变和骨骼肌代谢的改变。纠正这些疾病的方法对于发展ALS的治疗策略很有希望。