Hosseinibarkooie Seyyedmohsen, Schneider Svenja, Wirth Brunhilde
a Institute of Human Genetics , University of Cologne , Cologne , Germany.
b Center for Molecular Medicine Cologne , University of Cologne , Cologne , Germany.
Expert Rev Proteomics. 2017 Jul;14(7):581-592. doi: 10.1080/14789450.2017.1345631. Epub 2017 Jun 30.
Spinal muscular atrophy (SMA) is a neurodegenerative disorder characterized by alpha motor neuron loss in the spinal cord due to reduced survival motor neuron (SMN) protein level. While the genetic basis of SMA is well described, the specific molecular pathway underlying SMA is still not fully understood. Areas covered: This review discusses the recent advancements in understanding the molecular pathways in SMA using different omics approaches and genetic modifiers identified in both vertebrate and invertebrate systems. The findings that are summarized in this article were deduced from original articles and reviews with a particular focus on the latest advancements in the field. Expert commentary: The identification of genetic modifiers such as PLS3 and NCALD in humans or of SMA modulators such as Elavl4 (HuD), Copa, Uba1, Mapk10 (Jnk3), Nrxn2 and Tmem41b (Stasimon) in various SMA animal models improved our knowledge of impaired cellular pathways in SMA. Inspiration from modifier genes and their functions in motor neuron and neuromuscular junctions may open a new avenue for future SMA combinatorial therapies.
脊髓性肌萎缩症（SMA）是一种神经退行性疾病，其特征是由于存活运动神经元（SMN）蛋白水平降低，导致脊髓中的α运动神经元丧失。虽然SMA的遗传基础已得到充分描述，但SMA潜在的具体分子途径仍未完全了解。涵盖领域：本综述讨论了使用不同的组学方法以及在脊椎动物和无脊椎动物系统中鉴定出的遗传修饰因子来理解SMA分子途径方面的最新进展。本文总结的研究结果源自原始文章和综述，特别关注该领域的最新进展。专家评论：在人类中鉴定出如PLS3和NCALD等遗传修饰因子，或在各种SMA动物模型中鉴定出如Elavl4（HuD）、Copa、Uba1、Mapk10（Jnk3）、Nrxn2和Tmem41b（Stasimon）等SMA调节因子，提高了我们对SMA中受损细胞途径的认识。修饰基因及其在运动神经元和神经肌肉接头中的功能所带来的启发，可能为未来SMA的联合治疗开辟一条新途径。
