Browne Susan E, Beal M Flint
Department of Neurology and Neuroscience, A-502, Weill Medical College of Cornell University, 525 East 68th Street, New York, New York 10021, USA.
Neurochem Res. 2004 Mar;29(3):531-46. doi: 10.1023/b:nere.0000014824.04728.dd.
Huntington's disease (HD) is a hereditary neurodegenerative disorder that gradually robs sufferers of the ability to control movements and induces psychological and cognitive impairments. This devastating, lethal disease is one of several neurological disorders caused by trinucleotide expansions in affected genes, including spinocerebellar ataxias, dentatorubral-pallidoluysian atrophy, and spinal bulbar muscular atrophy. HD symptoms are associated with region-specific neuronal loss within the central nervous system, but to date the mechanism of this selective cell death remains unknown. Strong evidence from studies in humans and animal models suggests the involvement of energy metabolism defects, which may contribute to excitotoxic processes, oxidative dmage, and altered gene regulation. The development of transgenic mouse models expressing the human HD mutation has provided novel opportunities to explore events underlying selective neuronal death in HD, which has hitherto been impossible in humans. Here we discuss how animal models are redefining the role of energy metabolism in HD etiology.
亨廷顿舞蹈症（HD）是一种遗传性神经退行性疾病，它会逐渐剥夺患者控制运动的能力，并引发心理和认知障碍。这种具有毁灭性的致命疾病是由受影响基因中的三核苷酸重复扩增引起的几种神经疾病之一，包括脊髓小脑共济失调、齿状核红核苍白球路易体萎缩症和脊髓延髓肌肉萎缩症。HD症状与中枢神经系统内特定区域的神经元丢失有关，但迄今为止，这种选择性细胞死亡的机制仍不清楚。来自人类和动物模型研究的有力证据表明能量代谢缺陷与之相关，这可能导致兴奋毒性过程、氧化损伤和基因调控改变。表达人类HD突变的转基因小鼠模型的开发为探索HD中选择性神经元死亡背后的事件提供了新机会，而这在人类中迄今为止是不可能实现的。在此，我们讨论动物模型如何重新定义能量代谢在HD病因学中的作用。
