Sica Roberto E
Science and Technological Division and Instituto de Investigaciones Cardiológicas, Department of Neurology (ININCA), Medical School, Buenos Aires University, Argentina.
Med Hypotheses. 2015 May;84(5):481-9. doi: 10.1016/j.mehy.2015.02.004. Epub 2015 Feb 10.
Most of the named primary degenerative diseases of the human central nervous system have been attributed to a direct, primary damage of some particular population of neurons. Within the spectrum of these illnesses there are disorders like amyotrophic lateral sclerosis, fronto-temporal dementia, Alzheimer's dementia, Parkinson's disease, Huntington's dementia and cerebellar ataxias affecting exclusively the human species. In the last years it has been shown that non-neural cells, mainly astrocytes, have a crucial role in the starting and development of these diseases. We suggest that the causative agent of these illnesses gets home first within the astrocytes, rather than the neurons, making them sick by modifying the structure of some proteins; from these cells the abnormal process would start a trip to other astrocytes having the same genetic, metabolic, structural and functional profiles that the originally affected astrocytes have, going through the gap junctions which connect that particular population devoted to a particular set of neurons. This appears to be a likely hypothesis because the astrocytes related to a defined population of neurons have their own, private properties and characteristics needed to support one particular set of neurons performing a defined function, making them a different and unique population, a fact which would limit the spreading of the disease to those astrocytes, sparing other astrocyte populations which do not share those characteristics. If this were the mechanism underlying these illnesses, the neurons, which their health depends on those astrocytes, would be deprived of their patronage and would start all the changes that characterizes a programmed cell death, and the clinical manifestations of a defined pathology would consequently appear.
人类中枢神经系统的大多数命名原发性退行性疾病都被归因于某些特定神经元群体的直接原发性损伤。在这些疾病范围内，有诸如肌萎缩侧索硬化症、额颞叶痴呆、阿尔茨海默病痴呆、帕金森病、亨廷顿病痴呆和仅影响人类的小脑共济失调等病症。近年来已表明，非神经细胞，主要是星形胶质细胞，在这些疾病的起始和发展中起关键作用。我们认为，这些疾病的病原体首先进入星形胶质细胞而非神经元，通过改变某些蛋白质的结构使其患病；异常过程将从这些细胞开始，通过连接特定神经元群体的缝隙连接，传播到具有与最初受影响的星形胶质细胞相同的遗传、代谢、结构和功能特征的其他星形胶质细胞。这似乎是一个合理的假设，因为与特定神经元群体相关的星形胶质细胞具有支持执行特定功能的特定神经元群体所需的自身独特属性和特征，这使它们成为一个不同且独特的群体，这一事实会限制疾病传播到那些星形胶质细胞，而使不具有这些特征的其他星形胶质细胞群体不受影响。如果这是这些疾病的潜在机制，那么其健康依赖于那些星形胶质细胞的神经元将被剥夺支持，并将开始所有程序性细胞死亡的特征性变化，相应地就会出现特定病理的临床表现。
