Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are neurodegenerative diseases with overlapping clinical phenotypes based on impaired motoneuron function. However, the pathomechanisms of both diseases are largely unknown, and it is still unclear whether they converge on the molecular level. SMA is a monogenic disease caused by low levels of functional Survival of Motoneuron (SMN) protein, whereas ALS involves multiple genes as well as environmental factors. Recent evidence argues for involvement of actin regulation as a causative and dysregulated process in both diseases. ALS-causing mutations in the actin-binding protein profilin-1 as well as the ability of the SMN protein to directly bind to profilins argue in favor of a common molecular mechanism involving the actin cytoskeleton. Profilins are major regulat ors of actin-dynamics being involved in multiple neuronal motility and transport processes as well as modulation of synaptic functions that are impaired in models of both motoneuron diseases. In this article, we review the current literature in SMA and ALS research with a focus on the actin cytoskeleton. We propose a common molecular mechanism that explains the degeneration of motoneurons for SMA and some cases of ALS.

肌萎缩性侧索硬化症（ALS）和脊髓性肌萎缩症（SMA）是神经退行性疾病，具有基于运动神经元功能受损的临床表型重叠的现象。然而，这两种疾病的致病机理在很大程度上尚不清楚，并且尚不清楚它们是否在分子水平上趋同。SMA是一种单基因疾病，是由Motonuron（SMN）蛋白的低功能生存水平引起的，而ALS涉及多个基因以及环境因素。最近的证据表明肌动蛋白调节参与这两种疾病的致病性和失调过程。肌动蛋白结合蛋白profilin-1中引起ALS的突变，以及SMN蛋白直接结合到蛋白纤维蛋白上的能力，都主张一种涉及肌动蛋白细胞骨架的常见分子机制。脯氨酸蛋白是肌动蛋白动力学的主要调节因子，参与多种神经元运动和转运过程以及突触功能的调节，这两种运动神经元疾病模型均受损。在本文中，我们回顾了有关SMA和ALS研究的最新文献，重点是肌​​动蛋白的细胞骨架。我们提出了一个共同的分子机制来解释SMA和某些ALS的运动神经元的退化。