Studies of Hereditary Neurological Disease: Disease Mechanisms

这项研究计划的目的是探讨遗传性神经疾病的机制，最终目的是开发这些疾病的有效治疗方法。最近的研究集中在三种特定的神经肌肉疾病上：由于SMN蛋白缺乏引起的常染色体隐性脊肌萎缩症(SMA)，由于雄激素受体多聚谷氨酰胺扩张引起的X连锁脊髓和延髓肌萎缩(SBMA)，以及由ZASP基因突变引起的肌纤维肌病。过去一年的具体研究成果包括：(1)蛋白酶体抑制剂在SMA小鼠模型中的治疗效果评估；(2)IGF-1在SBMA动物模型中的作用表征；(3)野生型和突变型ZASP相互作用蛋白的鉴定，以及ZASP突变动物模型的建立。

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.