A UNIFYING HYPOTHESIS FOR THE CAUSE OF AMYOTROPHIC LATERAL SCLEROSIS, PARKINSONISM, AND ALZHEIMER-DISEASE
A UNIFYING HYPOTHESIS FOR THE CAUSE OF AMYOTROPHIC LATERAL SCLEROSIS, PARKINSONISM, AND ALZHEIMER-DISEASE
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DOI：
10.1002/ana.410100602
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发表时间：
1981-01-01
影响因子：
11.2
通讯作者：
APPEL, SH
中科院分区：
文献类型：
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作者：
APPEL, SH
肌萎缩性侧索硬化症、帕金森病和阿尔茨海默病的病因尚不清楚。此外，其中两种疾病几乎完全得不到治疗。该论文提出，这些疾病中的每一种都是由于缺乏疾病特异性神经营养激素。这种激素会在受影响的神经元的目标中被加工或储存。它会被突触后细胞释放，然后在被突触前末梢摄取后以逆行的方式发挥作用。在肌萎缩侧索硬化症的下运动神经元综合征中，肌肉细胞不能释放适当的运动神经营养激素将导致前角细胞功能受损。在帕金森病中，神经营养功能衰竭的特征是纹状体细胞无法提供所需的多巴胺神经营养激素，从而导致黑质细胞受损。在阿尔茨海默病中，异常将在于海马和皮质细胞不能提供相关的胆碱能神经营养激素，导致内侧隔和基底核神经元受损。中枢神经系统组织培养提供了一个方便的系统，其中测定这些神经营养激素，并应允许测试的假设。
The causes of amyotrophic lateral sclerosis, Parkinson disease, and Alzheimer disease are unknown. Furthermore, treatment for two of these conditions is almost totally lacking. The thesis is presented that each of these disorders is due to lack of a disorder‐specific neurotrophic hormone. The hormone would be elaborated or stored in the target of the affected neurons. It would be released by the postsynaptic cell and then exert its effect in a retrograde fashion after being taken up by the presynaptic terminal. In the lower motor neuron syndromes of amyotrophic lateral sclerosis, failure of muscle cells to release the appropriate motor neuron syndromes of amyotrophic lateral sclerosis, failure of muscle cells to release the appropriate motor neurotrophic hormone would result in impaired function of anterior horn cells. In Parkinson disease, the neurotrophic failure would be characterized by inability of striatal cells to provide the required dopamine neurotrophic hormone with resulting impairment of substantia nigra cells. In Alzheimer disease, the abnormalities would lie in failure of the hippocampus and cortical cells to supply the relevant cholinergic neurotrophic hormone with resulting impairment of medial septal and nucleus basalis neurons. Central nervous system tissue culture provides a convenient system in which to assay these neurotrophic hormones and should permit a test of the hypothesis.