The Stacey Motor Neuron Disease Laboratory, Department of Pathology D06, Sydney Medical School, The University of Sydney, New South Wales 2006, Australia.
Med Hypotheses. 2011 Oct;77(4):544-7. doi: 10.1016/j.mehy.2011.06.027. Epub 2011 Jul 2.
The major neurodegenerative diseases (Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis) share in common a mostly sporadic occurrence, a focal onset of pathology, and spread from the initial site of injury to adjacent regions of the nervous system. The sporadic nature and focal onset of these diseases can be explained either by somatic mutations (arising in either of two models of cell lineage) or environmental agents, both of which affect a small number of neurons. The genetic or environmental agent then changes the conformation of a vital protein in these neurons. Spread of the diseases occurs by the misfolded proteins being transferred to adjacent neurons. Clinical and pathological details of one neurodegenerative disorder, amyotrophic lateral sclerosis, are presented to show how the pathogenesis of a typical neurodegenerative disease can be explained by this "somatic-spread" hypothesis. Ultrasensitive techniques will be needed to detect the initiating genetic or environmental differences that are predicted to be present in only a few cells.
主要的神经退行性疾病（阿尔茨海默病、帕金森病和肌萎缩侧索硬化症）具有共同的特点，即大多数为散发性疾病，病理起始部位局限，从初始损伤部位向神经系统的邻近区域扩散。这些疾病的散发性和局限性发作可以通过体细胞突变（出现在两种细胞谱系模型中的任何一种）或环境因素来解释，这两者都会影响少数神经元。然后，遗传或环境因素改变了这些神经元中一种重要蛋白质的构象。疾病的传播是通过错误折叠的蛋白质转移到邻近的神经元来实现的。本文介绍了一种神经退行性疾病——肌萎缩侧索硬化症的临床和病理细节，以说明这种“体传播”假说如何解释典型神经退行性疾病的发病机制。需要超灵敏技术来检测仅存在于少数细胞中的起始遗传或环境差异。
