Molecular Mechanisms of Neurodegeneration in Spinal Muscular Atrophy.
Molecular Mechanisms of Neurodegeneration in Spinal Muscular Atrophy.
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DOI：
10.4137/jen.s33122
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发表时间：
2016
影响因子：
--
通讯作者：
Gangwani L
中科院分区：
文献类型：
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作者：
Ahmad S;Bhatia K;Kannan A;Gangwani L
脊髓性肌萎缩症（SMA）是一种常染色体隐性遗传的运动神经元疾病，发病率高，是婴儿死亡的最常见遗传原因。SMA的主要特征是脊髓运动神经元变性，导致骨骼肌萎缩，随后出现对称性肢体瘫痪、呼吸衰竭和死亡。在人类中，生存运动神经元1（SMN1）基因突变将SMN蛋白的表达负荷转移到SMN2基因，后者由于选择性剪接而产生低水平的全长SMN蛋白，这足以促进胚胎发育和存活，但会导致SMA。（a）SMN基因表达的调节和（B）由低水平SMN引起的运动神经元变性的分子机制尚不清楚。然而，近年来取得了一些进展，为理解SMA发病机制的细胞和分子基础提供了新的见解。在这篇综述中，我们简要总结了最近的进展，了解SMN水平的调节和信号转导机制，介导SMA神经变性的分子机制。
Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease with a high incidence and is the most common genetic cause of infant mortality. SMA is primarily characterized by degeneration of the spinal motor neurons that leads to skeletal muscle atrophy followed by symmetric limb paralysis, respiratory failure, and death. In humans, mutation of the Survival Motor Neuron 1 (SMN1) gene shifts the load of expression of SMN protein to the SMN2 gene that produces low levels of full-length SMN protein because of alternative splicing, which are sufficient for embryonic development and survival but result in SMA. The molecular mechanisms of the (a) regulation of SMN gene expression and (b) degeneration of motor neurons caused by low levels of SMN are unclear. However, some progress has been made in recent years that have provided new insights into understanding of the cellular and molecular basis of SMA pathogenesis. In this review, we have briefly summarized recent advances toward understanding of the molecular mechanisms of regulation of SMN levels and signaling mechanisms that mediate neurodegeneration in SMA.