Tippett Lynette J, Waldvogel Henry J, Snell Russell G, Vonsattel Jean-Paul, Young Anne B, Faull Richard L M
Centre for Brain Research, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
School of Psychology, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Adv Neurobiol. 2017;15:129-161. doi: 10.1007/978-3-319-57193-5_5.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by extensive neuronal loss in the striatum and cerebral cortex, and a triad of clinical symptoms affecting motor, cognitive/behavioural and mood functioning. The mutation causing HD is an expansion of a CAG tract in exon 1 of the HTT gene. This chapter provides a multifaceted overview of the clinical complexity of HD. We explore recent directions in molecular genetics including the identification of loci that are genetic modifiers of HD that could potentially reveal therapeutic targets beyond the HTT gene transcript and protein. The variability of clinical symptomatology in HD is considered alongside recent findings of variability in cellular and neurochemical changes in the striatum and cerebral cortex in human brain. We review evidence from structural neuroimaging methods of progressive changes of striatum, cerebral cortex and white matter in pre-symptomatic and symptomatic HD, with a particular focus on the potential identification of neuroimaging biomarkers that could be used to test promising disease-specific and modifying treatments. Finally we provide an overview of completed clinical trials in HD and future therapeutic developments.
亨廷顿舞蹈症（HD）是一种常染色体显性神经退行性疾病，其特征是纹状体和大脑皮层中广泛的神经元丢失，以及影响运动、认知/行为和情绪功能的三联征临床症状。导致HD的突变是HTT基因外显子1中CAG序列的扩增。本章对HD的临床复杂性进行了多方面概述。我们探讨了分子遗传学的最新方向，包括对HD基因修饰位点的鉴定，这些位点可能揭示除HTT基因转录本和蛋白质之外的治疗靶点。HD临床症状学的变异性与人类大脑纹状体和大脑皮层中细胞和神经化学变化变异性的最新发现一同被考虑。我们回顾了来自结构神经成像方法的证据，这些证据表明在症状前和有症状的HD中，纹状体、大脑皮层和白质会发生渐进性变化，特别关注潜在的神经成像生物标志物的识别，这些生物标志物可用于测试有前景的疾病特异性和修饰性治疗方法。最后，我们概述了HD已完成的临床试验以及未来的治疗进展。
