Applied Biopsychology Program, Department of Psychology, University of New Orleans, New Orleans, Louisiana, United States of America.
PLoS One. 2013;8(1):e53606. doi: 10.1371/journal.pone.0053606. Epub 2013 Jan 21.
Huntington's disease (HD) is a neuropsychiatric disorder characterized by choreiform movement of the limbs, cognitive disability, psychosis and dementia. It is invariably associated with an abnormally long CAG expansion within the IT15 gene on human chromosome 4. Although the mutant huntingtin protein is ubiquitously expressed in HD patients, cellular degeneration occurs predominantly in neurons within the corpus striatum and cerebral cortex. The Ras homolog Rhes is expressed very selectively in the precise brain areas affected by HD. Recent in vitro work suggests that Rhes may be a co-factor with mutant huntingtin in cell death. The objective of the present study was to examine whether the inhibition of Rhes would attenuate or delay the symptoms of HD in vivo. We used a transgenic mouse model of HD crossed with Rhes knockout mice to show that the behavioral symptoms of HD are regulated by Rhes. HD(+)/Rhes(-/-) mice showed significantly delayed expression of HD-like symptoms in this in vivo model. Drugs that block or inhibit the actions of Rhes may be useful as the first treatments for HD.
亨廷顿舞蹈病（HD）是一种神经精神障碍，其特征为四肢舞蹈样运动、认知障碍、精神病和痴呆。它总是与人类 4 号染色体 IT15 基因内异常长的 CAG 扩展有关。尽管突变的亨廷顿蛋白在 HD 患者中广泛表达，但细胞退化主要发生在纹状体和大脑皮层的神经元中。Ras 同源物 Rhes 在受 HD 影响的确切脑区选择性表达。最近的体外研究表明，Rhes 可能是细胞死亡中与突变亨廷顿蛋白的共同因子。本研究的目的是检查抑制 Rhes 是否会减轻或延迟体内 HD 的症状。我们使用了一种与 Rhes 基因敲除小鼠杂交的 HD 转基因小鼠模型，以表明 Rhes 调节 HD 的行为症状。在这种体内模型中，HD(+)/Rhes(-/-) 小鼠显示出 HD 样症状的表达明显延迟。阻断或抑制 Rhes 作用的药物可能作为 HD 的第一种治疗方法有用。
