Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.
Int J Biochem Cell Biol. 2011 Jan;43(1):20-4. doi: 10.1016/j.biocel.2010.10.014. Epub 2010 Nov 4.
Huntington's disease is an autosomal dominant genetic neurodegenerative disorder, which is characterized by progressive motor dysfunction, emotional disturbances, dementia, and weight loss. The disease is caused by pathological CAG-triplet repeat extension(s), encoding polyglutamines, within the gene product, huntingtin. Huntingtin is ubiquitously expressed through the body and is a protein of uncertain molecular function(s). Mutant huntingtin, containing pathologically extended polyglutamines causes the earliest and most dramatic neuropathologic changes in the neostriatum and cerebral cortex. Extended polyglutamines confer structural conformational changes to huntingtin, which gains novel properties, resulting in aberrant interactions with multiple cellular components. The diverse and variable aberrations mediated by mutant huntingtin perturb many cellular functions essential for neuronal homeostasis and underlie pleiotropic mechanisms of Huntington's disease pathogenesis. The only approved drug for Huntington's disease is a symptomatic treatment, tetrabenazine; thus, novel neuroprotective strategies, slowing, blocking and possibly reversing disease progression, are vital for developing effective therapies.
亨廷顿病是一种常染色体显性遗传的神经退行性疾病，其特征是进行性运动功能障碍、情绪紊乱、痴呆和体重减轻。该疾病是由基因产物亨廷顿内病理性 CAG-三核苷酸重复扩展（编码多聚谷氨酰胺）引起的。亨廷顿在体内广泛表达，是一种功能未知的蛋白质。含有病理性扩展多聚谷氨酰胺的突变亨廷顿导致新纹状体和大脑皮层出现最早和最显著的神经病理学变化。扩展的多聚谷氨酰胺使亨廷顿发生结构构象变化，获得新的特性，导致与多种细胞成分的异常相互作用。突变亨廷顿介导的多种和可变的异常扰乱了许多对神经元内稳态至关重要的细胞功能，并构成亨廷顿病发病机制的多种机制。唯一批准用于亨廷顿病的药物是对症治疗药物——四苯嗪；因此，开发有效的治疗方法需要新型神经保护策略，包括减缓、阻断和可能逆转疾病进展。
