Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease
Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease
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DOI：
10.1523/jneurosci.15-11-07727.1995
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发表时间：
1995-11
期刊：
影响因子：
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通讯作者：
Y. Sagot;M. Dubois‐Dauphin;S. Tan;F. de Bilbao;P. Aebischer;J. Martinou;A. Kato
中科院分区：
文献类型：
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作者：
Y. Sagot;M. Dubois‐Dauphin;S. Tan;F. de Bilbao;P. Aebischer;J. Martinou;A. Kato
在几种实验情况下，bcl2及其类似物保护不同类别的神经元免受凋亡。因此，这些蛋白质可能会为治疗神经退行性疾病提供一种手段。我们在运动神经元病(进行性运动神经元病/PMN)遗传性小鼠模型中检测了Bcl-2过表达的影响。PMN/PMN小鼠失去运动神经元和有髓轴突，并在6周龄时死亡。当这些小鼠与过量表达人bcl2的转基因小鼠杂交时，面部运动神经元得到了挽救，同时恢复了它们正常的胞体大小和胆碱乙酰转移酶的表达。然而，Bcl2的过度表达并不能阻止面神经和膈运动神经中有髓轴突的退化，也不能延长动物的寿命。由于在PMN/PMN/bcl2小鼠中，bcl2严格作用于神经元胞体存活而不补偿神经退行性变，这种原癌基因本身不足以治疗以轴突损伤为主要成分的神经退行性疾病。
Bcl-2 and its analogs protect different classes of neurons from apoptosis in several experimental situations. These proteins may therefore provide a means for treatment of neurodegenerative diseases. We examined the effects of Bcl-2 overexpression in a genetic mouse model with motor neuron disease (progressive motor neuronopathy/pmn). Pmn/pmn mice lose motoneurons and myelinated axons, and die at 6 weeks of age. When these mice were crossed with transgenic mice that overexpress human Bcl-2, there was a rescue of the facial motoneurons with a concomitant restoration of their normal soma size and expression of choline acetyltransferase. However, Bcl-2 overexpression did not prevent degeneration of myelinated axons in the facial and phrenic motor nerves and it did not increase the life span of the animals. Since Bcl-2 acts strictly on neuronal cell body survival without compensating for nerve degeneration in pmn/pmn/bcl-2 mice, this proto- oncogene would not in itself be sufficient for treatment of neurodegenerative diseases where axonal impairment is a major component.