Department of Social Medicine, Poznan University of Medical Sciences Poznan, Poland.
MRC National Institute for Medical Research London, UK.
Front Physiol. 2014 Oct 6;5:380. doi: 10.3389/fphys.2014.00380. eCollection 2014.
Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by the expansion of a polyglutamine stretch within the huntingtin protein (HTT). The neurological symptoms, that involve motor, cognitive and psychiatric disturbances, are caused by neurodegeneration that is particularly widespread in the basal ganglia and cereberal cortex. HTT is ubiquitously expressed and in recent years it has become apparent that HD patients experience a wide array of peripheral organ dysfunction including severe metabolic phenotype, weight loss, HD-related cardiomyopathy and skeletal muscle wasting. Although skeletal muscles pathology became a hallmark of HD, the mechanisms underlying muscular atrophy in this disorder are unknown. Skeletal muscles account for approximately 40% of body mass and are highly adaptive to physiological and pathological conditions that may result in muscle hypertrophy (due to increased mechanical load) or atrophy (inactivity, chronic disease states). The atrophy is caused by degeneration of myofibers and their replacement by fibrotic tissue is the major pathological feature in many genetic muscle disorders. Under normal physiological conditions the muscle function is orchestrated by a network of intrinsic hypertrophic and atrophic signals linked to the functional properties of the motor units that are likely to be imbalanced in HD. In this article, we highlight the emerging field of research with particular focus on the recent studies of the skeletal muscle pathology and the identification of new disease-modifying treatments.
亨廷顿病（HD）是一种遗传性神经退行性疾病，由亨廷顿蛋白（HTT）内的多聚谷氨酰胺延伸引起。涉及运动、认知和精神障碍的神经症状是由神经退行性变引起的，这种退行性变在基底神经节和大脑皮层中特别广泛。HTT 广泛表达，近年来，人们已经清楚地认识到 HD 患者会出现多种外周器官功能障碍，包括严重的代谢表型、体重减轻、与 HD 相关的心肌病和骨骼肌消耗。尽管骨骼肌病理学已成为 HD 的标志，但该疾病中肌肉萎缩的机制尚不清楚。骨骼肌约占体重的 40%，对生理和病理条件具有高度适应性，这些条件可能导致肌肉肥大（由于机械负荷增加）或萎缩（不活动、慢性疾病状态）。萎缩是由肌纤维变性和纤维组织取代引起的，这是许多遗传性肌肉疾病的主要病理特征。在正常生理条件下，肌肉功能由内在肥大和萎缩信号网络协调，这些信号与运动单位的功能特性相关，而在 HD 中这些信号可能会失衡。本文强调了新兴的研究领域，特别是最近对骨骼肌病理学和新的疾病修饰治疗的研究。
