Gárdián G, Vécsei L
Department of Neurology, University of Szeged, Szeged, Hungary.
J Neural Transm (Vienna). 2004 Oct;111(10-11):1485-94. doi: 10.1007/s00702-004-0201-4.
Huntington's disease is an autosomal dominantly inherited progressive neurodegenerative disorder. The mutant gene has been localised to chromosome 4p16.3. The gene product huntingtin is widely distributed in both neurones and extraneuronal tissues. The mutation in Huntington's disease involves the expansion of a trinucleotide (CAG) repeat encoding glutamine. The etiology of Huntington's disease is yet unknown but increasing evidence suggests important role of altered gene transcription, mitochondrial dysfunction and excitotoxicity. The expanded polyglutamine stretch leads to a conformational change and abnormal protein-protein interactions. Mutant huntingtin can bind to transcription factors, resulting in reduced levels of acetylated histones. One consequence of this appears to be a decreased expression of genes which may play critical roles in neuronal survival. To date, a number of palliative therapies have been demonstrated to be effective in reducing the motor features, and particularly the chorea, but no treatment is at hand for the other symptoms of Huntington's disease. However, these treatments produce very limited symptomatic benefit. In the absence of disease-modifying treatment, the other avenue is the neural transplantation.However, recent advances in understanding have furnished new hope that a therapeutic strategy may one day be possible.
亨廷顿舞蹈症是一种常染色体显性遗传的进行性神经退行性疾病。突变基因已定位到4号染色体的p16.3区域。该基因产物亨廷顿蛋白广泛分布于神经元和神经外组织中。亨廷顿舞蹈症的突变涉及编码谷氨酰胺的三核苷酸（CAG）重复序列的扩增。亨廷顿舞蹈症的病因尚不清楚，但越来越多的证据表明基因转录改变、线粒体功能障碍和兴奋性毒性起着重要作用。扩增的多聚谷氨酰胺序列会导致构象变化和异常的蛋白质-蛋白质相互作用。突变的亨廷顿蛋白可与转录因子结合，导致乙酰化组蛋白水平降低。其结果之一似乎是可能对神经元存活起关键作用的基因表达减少。迄今为止，已证明多种姑息疗法在减轻运动症状，尤其是舞蹈症方面有效，但尚无针对亨廷顿舞蹈症其他症状的治疗方法。然而，这些治疗产生的症状改善非常有限。在缺乏疾病修正治疗的情况下，另一条途径是神经移植。然而，最近在认识上的进展带来了新的希望，即有朝一日可能实现一种治疗策略。
