Venetian Institute of Molecular Medicine, Padova, Italy.
Biofactors. 2011 May-Jun;37(3):206-18. doi: 10.1002/biof.162. Epub 2011 Jun 14.
Huntington's disease (HD) is caused by a mutation that increases the number of CAG repeats in the gene encoding for the protein Huntingtin (Htt). The mutation results in the pathological expansion of the polyQ stretch that is normally present within the N-terminal region of Htt. Even if Htt is ubiquitously expressed in tissues, the changes in the protein finally result in the clinical manifestation of motor and cognitive impairments observed in HD patients. The molecular ethiology of the disease is obscure: a number of cellular and animal models are used as essential tools in experimental approaches aimed at understanding it. Biochemical changes have been described that correlate with the malfunction of HD neurons (primarily in the striatum): consensus is gradually emerging that the dyshomeostasis of Ca(2+) and/or mitochondria stress are important factors in the linkage of the Htt mutation to the onset and progression of the disease. Here, we present a succint overview of the changes of Htt, of its possible effect on the transcription of critical genes and of its causative role in the disturbance of the neuronal Ca(2+) homeostasis. Particular emphasis will be placed on the role of mitochondria as key player in the molecular pathogenesis of the disease.
亨廷顿病（HD）是由编码 Huntingtin 蛋白（Htt）的基因中 CAG 重复次数增加引起的突变引起的。该突变导致多聚谷氨酰胺延伸病理性扩展，该延伸通常存在于 Htt 的 N 端区域内。即使 Htt 在组织中广泛表达，该蛋白的变化最终导致在 HD 患者中观察到的运动和认知障碍的临床表现。该疾病的分子发病机制尚不清楚：许多细胞和动物模型被用作实验方法的重要工具，旨在理解该疾病。已经描述了与 HD 神经元功能障碍相关的生化变化（主要在纹状体中）：逐渐达成共识的是，Ca(2+)和/或线粒体应激的失衡是 Htt 突变与疾病的发生和进展相关的重要因素。在这里，我们简要概述了 Htt 的变化，及其对关键基因转录的可能影响，以及其在神经元 Ca(2+)稳态紊乱中的因果作用。将特别强调线粒体作为该疾病分子发病机制中的关键因素的作用。
