Studies of Hereditary Neurological Disease: Disease Mechanisms

这项研究计划的目的是研究遗传性神经系统疾病的机制，最终目的是为这些疾病开发有效的治疗方法。研究重点是三种特定的运动神经元疾病：常染色体隐性脊髓性肌萎缩症（SMA），由于SMN蛋白缺乏，x -连锁脊髓和球性肌萎缩症（SBMA），由于雄激素受体中聚谷氨酰胺扩增，以及由tRNA合成酶突变引起的远端脊髓性肌萎缩/沙克-玛丽-牙病2D型（CMT2D）。在过去的一年中，具体的研究成果包括：(1)在SBMA细胞培养模型中表征IGF-1和Akt的作用；(2)评估组蛋白去乙酰化酶和蛋白酶体抑制剂治疗小鼠SMA模型的疗效；(3)CMT2D及其他遗传性神经病变和远端脊髓性肌萎缩的发病机制研究；(4)profilin在多谷氨酰胺病中的作用研究。

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. The research focuses on three specific motor neuron 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 distal spinal muscular atrophy/Charcot-Marie-Tooth disease type 2D (CMT2D) caused by mutations in tRNA synthetase. Specific research accomplishments in the past year include the following: (1) characterization of the role of IGF-1 and Akt in a cell culture model of SBMA, (2) evaluation of the efficacy of histone deacetylase and proteasome inhibitor treatment in a mouse model of SMA, (3) studies of the disease mechanisms of CMT2D and other hereditary forms of neuropathy and distal spinal muscular atrophy, (4) studies of the role of profilin in polyglutamine disease.