Merry D E, Kobayashi Y, Bailey C K, Taye A A, Fischbeck K H
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Hum Mol Genet. 1998 Apr;7(4):693-701. doi: 10.1093/hmg/7.4.693.
Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by the expansion of a polyglutamine repeat within the androgen receptor (AR). We have studied the mutant AR in an in vitro system, and find both aggregation and proteolytic processing of the AR protein to occur in a polyglutamine repeat length-dependent manner. In addition, we find the aberrant metabolism of expanded repeat AR to be coupled to cellular toxicity, indicating a likely molecular basis for the toxic gain of AR function that produces neuronal degeneration in SBMA.
脊髓延髓肌肉萎缩症（SBMA）是一种由雄激素受体（AR）内多聚谷氨酰胺重复序列扩增引起的神经退行性疾病。我们在体外系统中研究了突变型AR，发现AR蛋白的聚集和蛋白水解加工均以多聚谷氨酰胺重复序列长度依赖的方式发生。此外，我们发现扩增重复序列AR的异常代谢与细胞毒性相关，这表明在SBMA中产生神经元变性的AR功能毒性获得可能存在分子基础。
