van der Burg Jorien M M, Björkqvist Maria, Brundin Patrik
Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University BMC A10, Lund, Sweden.
Lancet Neurol. 2009 Aug;8(8):765-74. doi: 10.1016/S1474-4422(09)70178-4.
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a polyglutamine stretch in the huntingtin protein. Today, more than 15 years after the genetic defect underlying HD was discovered, the pathogenesis is still not well understood and there is no adequate treatment. Research into this disorder has conventionally focused on neurological symptoms and brain pathology, particularly neurodegeneration in the basal ganglia and cerebral cortex. Mutant huntingtin is, however, ubiquitously expressed throughout the body. Indeed, contrary to earlier thinking, HD is associated with abnormalities in peripheral tissues. These abnormal changes are not all secondary to brain dysfunction, but most seem to be directly caused by expression of mutant huntingtin in peripheral tissues. In this article, we highlight this emerging field of research and how it might affect our understanding of the pathogenesis of this disease, the development of novel biomarkers of disease progression, and the identification of new potential treatments.
亨廷顿舞蹈症（HD）是一种遗传性神经退行性疾病，由亨廷顿蛋白中的多聚谷氨酰胺延伸所致。如今，在导致HD的基因缺陷被发现15年多之后，其发病机制仍未被充分理解，也没有有效的治疗方法。对这种疾病的研究传统上集中在神经症状和脑病理学方面，特别是基底神经节和大脑皮层的神经退行性变。然而，突变型亨廷顿蛋白在全身普遍表达。事实上，与早期的观点相反，HD与外周组织的异常有关。这些异常变化并非都继发于脑功能障碍，而是大多数似乎直接由外周组织中突变型亨廷顿蛋白的表达引起。在本文中，我们重点介绍了这个新兴的研究领域，以及它可能如何影响我们对这种疾病发病机制的理解、疾病进展新生物标志物的开发，以及新潜在治疗方法的识别。
