Targeting the Ubiquitin Proteasome System to Treat Spinal Muscular Atrophy

 描述(申请人提供)：脊髓性肌萎缩症(SMA)是婴幼儿最常见的遗传性死亡原因。SMA是由于运动神经元1(SMN1)基因的缺失或突变导致广泛表达的SMN蛋白缺失所致。目前，对于SMA尚无有效的治疗方案。来自人类和啮齿动物的研究证据表明，增加中枢神经系统中SMN蛋白的水平足以改善疾病表型并延长生存时间。为了确定SMN蛋白水平的保护性修饰物，我们进行了全基因组RNAi筛选。我们在这个屏幕中识别的基因将使我们能够研究调节SMN蛋白水平的遗传修饰物和分子途径。这些靶点和途径应该为治疗SMA的治疗发展提供新的途径。

 DESCRIPTION (provided by applicant): Spinal muscular atrophy (SMA) is the most common inherited cause of death in infants and young children. SMA is caused by the deletion or mutation in the survival of motor neuron 1 (SMN1) gene, leading to a deficiency of the ubiquitously expressed SMN protein. Currently, there is no effective treatment option available for SMA. Evidence from studies in humans and rodents suggests that increasing SMN protein levels in the central nervous system is sufficient to ameliorate the disease phenotype and prolong survival. To identify protective modifiers of SMN protein levels we performed a genome-wide RNAi screen. Genes we identified in this screen will allow us to investigate genetic modifiers and molecular pathways that regulate SMN protein levels. These targets and pathways should provide novel avenues for therapeutic development for the treatment of SMA.