Studies of Hereditary Neurological Disease: Disease Mechanisms

遗传性神经系统疾病的研究：疾病机制

• 批准号: 8342259
• 负责人: Kenneth Fischbeck
• 金额: $ 168.98万
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8342259
• 关键词: Androgen Receptor; Animal Model; Binding; Bioavailable; Cell Culture Techniques; Disease; Evaluation; Genetic; Goals; IGF1 gene; Inherited; Insulin-Like Growth Factor I; Kennedy Syndrome; Link; Mediating; Modeling; Motor; Motor Neuron Disease; Mutation; Myopathy; Neuromuscular Diseases; Neuropathy; Proteasome Inhibitor; Protein Deficiency; Proteins; Research; Spinal Muscular Atrophy; Testing; Therapeutic Intervention; Toxic effect; Transgenic Animals; effective therapy; mouse model; mutant; nervous system disorder; polyglutamine; programs; protein degradation; spinal and bulbar muscular atrophy

The purpose of this research program is to investigate the mechanisms of hereditary neurological diseases, with the ultimate intent of developing effective treatments for these disorders. Recently, the research has focused on three specific neuromuscular diseases: autosomal recessive spinal muscular atrophy (SMA) due to deficiency of the protein SMN, X-linked spinal and bulbar muscular atrophy (SBMA) due to polyglutamine expansion in the androgen receptor, and myofibrillar myopathy caused by mutations in ZASP. Specific research accomplishments in the past year include the following: (1) evaluation of the effects of proteasome inhibitor treatment in a mouse model of SMA, (2) characterization of the effects of IGF-1 in an animal model of SBMA,(3) identification of interacting proteins for wild type and mutant ZASP and developing animal models with ZASP mutation.

该研究计划的目的是研究遗传性神经系统疾病的机制，最终目的是开发针对这些疾病的有效治疗方法。最近，该研究重点关注三种特定的神经肌肉疾病：由于 SMN 蛋白缺陷导致的常染色体隐性脊髓性肌萎缩症 (SMA)、由于雄激素受体中多谷氨酰胺扩张导致的 X 连锁脊髓和延髓性肌萎缩症 (SBMA) 以及肌原纤维ZASP 突变引起的肌病。过去一年的具体研究成果包括：(1) 评估蛋白酶体抑制剂治疗 SMA 小鼠模型的效果，(2) 表征 IGF-1 在 SBMA 动物模型中的作用，(3)鉴定野生型和突变型 ZASP 的相互作用蛋白并开发 ZASP 突变的动物模型。