Julien J P, Côté F, Collard J F
Centre for Research in Neuroscience, McGill University, Montreal General Hospital Research Institute, Canada.
Neurobiol Aging. 1995 May-Jun;16(3):487-90; discussion 490-2. doi: 10.1016/0197-4580(94)00169-2.
We discuss the evidence, based on the analysis of transgenic mice overexpressing the human neurofilament (NF) heavy gene, that abnormal NF accumulations can provoke neurodegeneration of motor neurons. Transgenic mice overexpressing by two-fold the normal levels of human NF-H proteins develop a progressive motor neuron disease with several pathologic features reminiscent of those found in amyotrophic lateral sclerosis (ALS). A plausible mechanism for the selective motor neuron degeneration is that exceeding levels of NF-H cross-linkages impede transport of newly synthesized NF structures. The abnormal NF accumulations in perikarya and proximal axons is accompanied by a disruption in axonal transport of not only NF proteins but also of other components required for maintenance of axons. The relevance of the NF-H transgenics as a model of ALS is discussed in light of our current knowledge of motor neuron disease.
我们基于对过表达人类神经丝（NF）重基因的转基因小鼠的分析，讨论了异常NF积累可引发运动神经元神经变性的证据。过表达水平为正常人类NF-H蛋白两倍的转基因小鼠会患上一种进行性运动神经元疾病，具有若干病理特征，使人联想到肌萎缩侧索硬化症（ALS）中发现的病理特征。选择性运动神经元变性的一个合理机制是，过量的NF-H交联会阻碍新合成的NF结构的运输。胞体和近端轴突中异常的NF积累不仅伴随着NF蛋白轴突运输的中断，还伴随着维持轴突所需的其他成分的轴突运输中断。根据我们目前对运动神经元疾病的了解，讨论了NF-H转基因小鼠作为ALS模型的相关性。
