Studies of Hereditary Neurological Disease: Disease Mechanisms

该研究计划的目的是调查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。该研究集中在三种特定的运动神经元疾病：由于蛋白SMN缺乏导致的常染色体隐性脊髓性肌萎缩症（SMA），由于雄激素受体中的多聚谷氨酰胺扩增导致的X连锁脊髓和延髓肌萎缩症（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疾病2D型（CMT 2D）。过去一年的具体研究成果包括：（1）在SBMA动物模型中组蛋白脱乙酰酶抑制和自噬的研究中的合作，（2）在SBMA细胞培养模型中IGF-1和Akt作用的表征，（3）在SMA小鼠模型中组蛋白脱乙酰酶治疗的功效的评估，（4）合作研究CMT 2D和其他遗传性神经病和远端脊髓性肌萎缩症的发病机制。

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.