T3S INSERM UMR 1124, Toxicité Environnementale, Cibles Thérapeutiques, Signalisation Cellulaire et Biomarqueurs, UFR des Sciences Fondamentales et Biomédicales, Campus Saint-Germain-des-prés, Université de Paris, Paris, France.
Centre de compétence maladies rares des pathologies neuromusculaires, service de génétique médicale, Hôpital Estaing, CHU Clermont-Ferrand, France.
Arch Pediatr. 2020 Dec;27(7S):7S3-7S8. doi: 10.1016/S0929-693X(20)30269-4.
Autosomal-recessive spinal muscular atrophy (SMA) is characterized by the loss of specific motor neurons of the spinal cord and skeletal muscle atrophy. SMA is caused by mutations or deletions of the survival motor neuron 1 (SMN1) gene, and disease severity correlates with the expression levels of the nearly identical copy gene, SMN2. Both genes ubiquitously express SMN protein, but SMN2 generates only low levels of protein that do not fully compensate for the loss-of-function of SMN1. SMN protein forms a multiprotein complex essential for the cellular assembly of ribonucleoprotein particles involved in diverse aspects of RNA metabolism. Other studies using animal models revealed a spatio-temporal requirement of SMN that is high during the development of the neuromuscular system and later, in the general maintenance of cellular and tissues homeostasis. These observations define a period for maximum therapeutic efficiency of SMN restoration, and suggest that cells outside the central nervous system may also participate in the pathogenesis of SMA. Finally, recent innovative therapies have been shown to mitigate SMN deficiency and have been approved to treat SMA patients. We briefly review major findings from the past twenty-five years of SMA research. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.
常染色体隐性脊髓性肌萎缩症（SMA）的特征是脊髓特定运动神经元的丧失和骨骼肌萎缩。SMA 是由生存运动神经元 1（SMN1）基因的突变或缺失引起的，疾病的严重程度与几乎相同的拷贝基因 SMN2 的表达水平相关。这两个基因都普遍表达 SMN 蛋白，但 SMN2 仅产生低水平的蛋白，无法完全弥补 SMN1 的功能丧失。SMN 蛋白形成一个多蛋白复合物，对于参与 RNA 代谢各个方面的核糖核蛋白颗粒的细胞组装至关重要。其他使用动物模型的研究揭示了 SMN 的时空需求，即在神经肌肉系统发育过程中以及后来的细胞和组织稳态维持中需求较高。这些观察结果定义了 SMN 恢复的最大治疗效率期，并表明中枢神经系统以外的细胞也可能参与 SMA 的发病机制。最后，最近的创新疗法已被证明可以减轻 SMN 缺乏，并已被批准用于治疗 SMA 患者。我们简要回顾了过去 25 年 SMA 研究的主要发现。©2020 法国儿科学会。由 Elsevier Masson SAS 出版。保留所有权利。
