STUDIES OF HEREDITARY NEUROLOGICAL DISEASE

神经遗传学分部的目的是调查遗传性神经疾病的原因，目的是为这些疾病开发有效的治疗方法。特别感兴趣的研究领域包括聚谷氨酰胺扩张性疾病(亨廷顿病、肯尼迪病和脊髓小脑性共济失调)、脊髓性肌萎缩症、夏科-玛丽-牙病、肌营养不良、遗传性运动神经元病和弗里德里希共济失调。在细胞培养和其他模型系统中对疾病机制进行了研究。一个相关的研究领域是雄激素对肌肉力量和运动神经元存活的影响机制。遗传外展计划旨在识别和描述患有遗传性神经疾病的患者和家庭的特征。庆大霉素治疗Duchenne肌营养不良症患者的试验已经完成，预计将进行进一步的治疗试验。过去一年的具体研究成果包括：(1)我们在聚谷氨酰胺扩张性神经退行性疾病的发病机制中涉及到一个关键的核因素。(2)我们在聚谷氨酰胺病的细胞培养模型中进一步表征了神经元死亡的途径。(3)我们已经在培养的神经元细胞中确定了雄激素刺激的特定因素，这是促进运动神经元存活的候选因素。(4)我们帮助缩小了分别定位于7号和9号染色体的常染色体显性轴索性神经病和运动神经元病的遗传缺陷的搜索范围。(5)我们研究了Friedreich共济失调患者的铁代谢异常，并帮助建立了这种疾病的小鼠模型。(6)我们对Duchenne肌营养不良患者进行了庆大霉素治疗的试验，发现MDX存在行为缺陷。这种疾病的小鼠模型。(7)我们已经建立了脊髓和延髓肌肉萎缩(肯尼迪病)的小鼠模型。(8)我们已经克隆了一种维生素C转运蛋白的基因，它可能涉及神经退行性疾病。

The purpose of the Neurogenetics Branch is to investigate the causes of hereditary neurological diseases, with the goal of developing effective treatments for these disorders. Particular areas of research interest include the polyglutamine expansion diseases (Huntington's disease, Kennedy's disease, and spinocerebellar ataxia), spinal muscular atrophy, Charcot-Marie-Tooth disease, muscular dystrophy, hereditary motor neuron disease, and Friedreich's ataxia. The disease mechanisms are studied in cell culture and other model systems. A related area of investigation is the mechanism of androgen effects on muscle strength and motor neuron survival. A genetic outreach program is intended to identify and characterize patients and families with hereditary neurological diseases. A trial of gentamicin treatment in patients with Duchenne muscular dystrophy has been completed, and further therapeutic trials are anticipated. Specific research accomplishments in the past year include the following:(1) We have implicated a critical nuclear factor in the pathogenesis of polyglutamine expansion neurodegenerative disease.(2) We have further characterized the pathway of neuronal death in a cell culture model of polyglutamine disease. (3) We have identified specific factors stimulated by androgens in cultured neuronal cells, which are candidates for promoting motor neuron survival.(4) We have helped to narrow the search for the genetic defects responsible for autosomal dominant forms of axonal neuropathy and motor neuronopathy that are mapped to chromosomes 7 and 9 respectively.(5) We have investigated abnormalities of iron metabolism in patients with Friedreich's ataxia, and helped in the creation of a mouse model for this disease.(6) We have carried out a trial of gentamicin treatment in patients with Duchenne muscular dystrophy, and identified a behavioral deficit in mdx, a mouse model for this disease.(7) We have created a mouse model of spinal and bulbar muscular atrophy (Kennedy's disease).(8) We have cloned the gene for a vitamin C transporter, which may be involved in neurodegenerative disease.