Targeting the Ubiquitin Proteasome System to Treat Spinal Muscular Atrophy

靶向泛素蛋白酶体系统治疗脊髓性肌萎缩症

基本信息

批准号：
9106740
负责人：
Barrington G Burnett
金额：
$ 30.37万
依托单位：
HENRY M. JACKSON FDN FOR THE ADV MIL/MED
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2020-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9106740
关键词：
Affect Biological Assay Cause of Death Cells Child Data Disease Enzymes Event Genes Genetic Human Induced Mutation Infant Infant Mortality Inherited Live Birth Longevity Mind Molecular Motor Motor Neuron Disease Motor Neurons Mutation Neuraxis Pathway interactions Patients Phosphoric Monoester Hydrolases Phosphotransferases Protein Isoforms Proteins Proteolysis RNA Splicing RNA interference screen Regulation Reporter Rodent Role SMN protein (spinal muscular atrophy)SMN2 gene Spinal Muscular Atrophy System Testing Therapeutic Ubiquitin Ubiquitination base disease phenotype effective therapy gene product genome-wide improved infant death loss of function mouse model multicatalytic endopeptidase complex neuromuscular new therapeutic target novel protein degradation public health relevance research study restoration small molecule spatiotemporal therapeutic development ubiquitin-protein ligase

项目摘要

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.

描述（由适用提供）：脊柱肌肉萎缩（SMA）是婴儿和幼儿中最常见的遗传死亡原因。 SMA是由运动神经元1（SMN1）基因存活中的缺失或突变引起的，导致无处不在表达的SMN蛋白的缺乏。当前，SMA尚无有效的治疗选择。来自人类和啮齿动物的研究的证据表明，中枢神经系统中SMN蛋白水平的提高足以改善疾病表型并延长生存率。为了鉴定SMN蛋白水平的受保护的修饰符，我们进行了全基因组RNAi筛选。我们在此屏幕上鉴定的基因将使我们能够研究调节SMN蛋白水平的遗传修饰剂和分子途径。这些靶标和途径应为治疗SMA的治疗发展提供新的途径。