STUDIES OF HEREDITARY NEUROLOGICAL DISEASE

神经遗传学科的目的是研究遗传性神经疾病的病因，目标是开发有效的治疗方法。研究兴趣的特定领域包括多谷氨酰胺扩张性疾病（亨廷顿氏病、肯尼迪氏病和脊髓小脑性共济失调）、脊髓性肌萎缩症、腓骨肌萎缩症、肌肉萎缩症、遗传性运动神经元疾病和弗里德赖希共济失调。在细胞培养和其他模型系统中研究疾病机制。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表征遗传神经疾病的患者和家庭。庆大霉素治疗杜氏肌营养不良患者的试验已经完成，并期待进一步的治疗试验。在过去的一年中，具体的研究成果包括：(1)我们发现了聚谷氨酰胺扩张性神经退行性疾病发病机制中的一个关键核因子。(2)我们在多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发现了雄激素刺激的特定因子，这些因子是促进运动神经元存活的候选因子。(4)我们已经帮助缩小了对常染色体显性轴突神经病变和运动神经病变的遗传缺陷的研究范围，这些遗传缺陷分别位于染色体7和9上。(5)我们研究了弗里德里希共济失调患者的铁代谢异常，并帮助建立了该疾病的小鼠模型。(6)我们对杜氏肌营养不良患者进行了庆大霉素治疗的试验，并在该疾病的小鼠模型mdx中发现了行为缺陷。我们建立了脊髓和球性肌肉萎缩（肯尼迪氏病）的小鼠模型。我们已经克隆了一种维生素C转运体的基因，它可能与神经退行性疾病有关。

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.