Center for Neurosciences, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, New York 11030, USA.
J Clin Invest. 2011 Feb;121(2):484-92. doi: 10.1172/JCI45646. Epub 2011 Feb 1.
Recent studies have focused on understanding the neural mechanisms underlying the emergence of clinical signs and symptoms in early stage Huntington disease (HD). Although cell-based assays have focused on cell autonomous effects of mutant huntingtin, animal HD models have revealed alterations in the function of neuronal networks, particularly those linking the cerebral cortex and striatum. These findings are complemented by metabolic imaging studies of disease progression in premanifest subjects. Quantifying metabolic progression at the systems level may identify network biomarkers to aid in the objective assessment of new disease-modifying therapies and identify new regions that merit mechanistic study in HD models.
最近的研究集中在理解亨廷顿病(HD)早期临床症状出现的神经机制。虽然基于细胞的测定法侧重于突变亨廷顿蛋白的细胞自主效应,但动物 HD 模型揭示了神经元网络功能的改变,特别是那些连接大脑皮层和纹状体的网络。这些发现得到了无症状受试者疾病进展代谢成像研究的补充。在系统水平上量化代谢进展可能会识别出网络生物标志物,以帮助对新的疾病修饰治疗进行客观评估,并确定在 HD 模型中值得进行机制研究的新区域。