Fischbeck K H, Lieberman A, Bailey C K, Abel A, Merry D E
Neurogenetics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Philos Trans R Soc Lond B Biol Sci. 1999 Jun 29;354(1386):1075-8. doi: 10.1098/rstb.1999.0461.
Kennedy's disease is an X-linked form of motor neuron disease caused by an expanded polyglutamine repeat in the androgen receptor. While the expansion mutation causes some loss of transcriptional activity by the androgen receptor, the predominant effect of expansion is probably a toxic gain of function, similar to the mechanism of other polyglutamine expansion diseases. Features of the neurodegenerative phenotype of Kennedy's disease have now been reproduced in transgenic animals and neuronal cell culture. Nuclear inclusions of mutant androgen receptor protein are found in these model systems and in autopsy samples from patients with Kennedy's disease.
肯尼迪病是一种X连锁的运动神经元疾病，由雄激素受体中多聚谷氨酰胺重复序列扩增引起。虽然扩增突变导致雄激素受体的转录活性有所丧失，但扩增的主要影响可能是功能获得性毒性，类似于其他多聚谷氨酰胺扩增疾病的机制。肯尼迪病神经退行性表型的特征现已在转基因动物和神经元细胞培养中得到重现。在这些模型系统以及肯尼迪病患者的尸检样本中发现了突变雄激素受体蛋白的核内包涵体。
