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）。具体研究的成就在过去的一年里包括以下几点:(1)合作研究的组蛋白deacteylase SBMA抑制和自噬在动物模型,(2)表征igf - 1的作用和Akt SBMA的细胞培养模型,(3)组蛋白脱乙酰酶治疗的疗效评价SMA的小鼠模型,(4)协作CMT2D的疾病机制的研究和其他遗传形式的神经病变和远端脊髓性肌萎缩。

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) collaboration in studies of histone deacteylase inhibition and autophagy in an animal model of SBMA, (2) characterization of the role of IGF-1 and Akt in a cell culture model of SBMA, (3) evaluation of the efficacy of histone deacetylase treatment in a mouse model of SMA, (4) collaboration in studies of the disease mechanisms of CMT2D and other hereditary forms of neuropathy and distal spinal muscular atrophy.