van Dellen Anton, Hannan Anthony J
University Laboratory of Physiology, University of Oxford, Parks Road, OX1 3PT, Oxford, UK.
Neurogenetics. 2004 Feb;5(1):9-17. doi: 10.1007/s10048-003-0169-5. Epub 2004 Jan 24.
Huntington's disease is a fatal inherited disorder in which there is progressive neurodegeneration in specific brain areas, mainly the striatum and cerebral cortex, producing motor, cognitive, and psychiatric symptoms. The trinucleotide repeat mutation involved is common to many other brain diseases, which may therefore involve similar mechanisms of pathogenesis. We are beginning to understand how a CAG trinucleotide repeat expansion in the disease gene, encoding an expanded polyglutamine tract, induces neuronal dysfunction and symptomatology in Huntington's disease. Recent evidence that environmental factors modify the onset and progression of neurodegeneration has shed new light on Huntington's disease and other devastating brain diseases. This review focuses on genetic mediators, environmental modulators, and associated gene-environment interactions in the pathogenesis of Huntington's disease.
亨廷顿舞蹈症是一种致命的遗传性疾病，特定脑区（主要是纹状体和大脑皮层）会出现进行性神经退行性变，从而产生运动、认知和精神症状。所涉及的三核苷酸重复突变在许多其他脑部疾病中也很常见，因此这些疾病可能涉及相似的发病机制。我们开始了解疾病基因中的CAG三核苷酸重复扩增如何导致编码的多聚谷氨酰胺序列延长，进而在亨廷顿舞蹈症中诱发神经元功能障碍和症状表现。最近有证据表明环境因素会影响神经退行性变的发病和进展，这为亨廷顿舞蹈症及其他毁灭性脑部疾病带来了新的认识。本综述聚焦于亨廷顿舞蹈症发病机制中的遗传介质、环境调节因子以及相关的基因 - 环境相互作用。
