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。研究集中在三种特定的运动神经元疾病上：由于SMN蛋白缺乏引起的常染色体隐性遗传性脊髓性肌萎缩症(SMA)，由于雄激素受体多聚谷氨酰胺扩张引起的X连锁脊髓和延髓性肌萎缩症(SBMA)，以及由tRNA合成酶突变引起的远端脊髓性肌萎缩症/Charcot-Marie-Tooth病2D型(CMT2D)。过去一年中取得的具体研究成果包括：(1)IGF-1和Akt在SBMA细胞培养模型中的作用的表征；(2)组蛋白脱乙酰酶和蛋白酶体抑制剂在SMA小鼠模型中的治疗效果的评估；(3)CMT2D及其他遗传型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的研究。

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.