Behavioral Neuroscience Program, Department of Psychology, Western Washington University, Bellingham, WA, USA.
Department of Medical and Molecular Genetics, King's College London, London, UK.
Lancet Neurol. 2015 Nov;14(11):1135-42. doi: 10.1016/S1474-4422(15)00177-5.
Huntington's disease is a genetic neurodegenerative disorder with symptoms that are linked to the progressive dysfunction and neuronal death in corticostriatal circuits. The causative gene (mutated HTT) is widely expressed outside the CNS and several peripheral signs of disease, including weight loss and increased proinflammatory signalling, are often seen; however, their importance in the pathophysiology of Huntington's disease is not clear. Studies in animals have shown that features of the disease involving the CNS, including synapse loss and behavioural alterations, are susceptible to modulation by treatments that target tissues and organs outside the CNS. Links between peripheral biology and neurodegeneration have also been shown in other chronic neurodegenerative diseases, suggesting that modulation of these peripheral targets can offer new approaches to therapeutic development. Treatments targeted to tissues and organs outside the CNS might therefore substantially improve the quality of life of patients with Huntington's disease, even in the absence of disease-modifying effects.
亨廷顿病是一种遗传性神经退行性疾病，其症状与皮质纹状体回路的进行性功能障碍和神经元死亡有关。致病基因（突变 HTT）在中枢神经系统外广泛表达，并且经常出现几种疾病的外周体征，包括体重减轻和促炎信号增加；然而，它们在亨廷顿病的病理生理学中的重要性尚不清楚。动物研究表明，涉及中枢神经系统的疾病特征，包括突触丧失和行为改变，易受针对中枢神经系统外组织和器官的治疗的调节。在其他慢性神经退行性疾病中也已经显示出外周生物学和神经退行性变之间的联系，这表明这些外周靶点的调节可以为治疗开发提供新的方法。因此，针对中枢神经系统外组织和器官的治疗方法可能会大大提高亨廷顿病患者的生活质量，即使没有疾病修饰作用。
