Goffin Luca, Lemoine Damien, Clotman Frédéric
Université catholique de Louvain, Louvain Institute of Biomolecular Science and Technology, Animal Molecular and Cellular Biology, Louvain-la-Neuve, Belgium.
Front Neurosci. 2024 Jul 18;18:1434404. doi: 10.3389/fnins.2024.1434404. eCollection 2024.
Amyotrophic lateral sclerosis (ALS) consists of a group of adult-onset fatal and incurable neurodegenerative disorders characterized by the progressive death of motor neurons (MNs) throughout the central nervous system (CNS). At first, ALS was considered to be an MN disease, caused by cell-autonomous mechanisms acting specifically in MNs. Accordingly, data from ALS patients and ALS animal models revealed alterations in excitability in multiple neuronal populations, including MNs, which were associated with a variety of cellular perturbations such as protein aggregation, ribonucleic acid (RNA) metabolism defects, calcium dyshomeostasis, modified electrophysiological properties, and autophagy malfunctions. However, experimental evidence rapidly demonstrated the involvement of other types of cells, including glial cells, in the etiopathogenesis of ALS through non-cell autonomous mechanisms. Surprisingly, the contribution of pre-motor interneurons (INs), which regulate MN activity and could therefore critically modulate their excitability at the onset or during the progression of the disease, has to date been severely underestimated. In this article, we review in detail how spinal pre-motor INs are affected in ALS and their possible involvement in the etiopathogenesis of the disease.
肌萎缩侧索硬化症（ALS）是一组成年发病的、致命且无法治愈的神经退行性疾病，其特征是整个中枢神经系统（CNS）中的运动神经元（MNs）逐渐死亡。起初，ALS被认为是一种MN疾病，由专门作用于MNs的细胞自主机制引起。因此，来自ALS患者和ALS动物模型的数据显示，包括MNs在内的多个神经元群体的兴奋性发生了改变，这与多种细胞扰动有关，如蛋白质聚集、核糖核酸（RNA）代谢缺陷、钙稳态失调、电生理特性改变和自噬功能障碍。然而，实验证据很快表明，包括胶质细胞在内的其他类型细胞通过非细胞自主机制参与了ALS的发病机制。令人惊讶的是，迄今为止，调节MN活动并因此可能在疾病发作或进展过程中严重调节其兴奋性的运动前中间神经元（INs）的作用被严重低估了。在本文中，我们详细综述了脊髓运动前INs在ALS中是如何受到影响的，以及它们可能参与该疾病的发病机制。
