An orally active anti-apoptotic molecule (CGP 3466B) preserves mitochondria and enhances survival in an animal model of motoneuron disease
An orally active anti-apoptotic molecule (CGP 3466B) preserves mitochondria and enhances survival in an animal model of motoneuron disease
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DOI：
10.1038/sj.bjp.0703633
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发表时间：
2000-10-01
影响因子：
7.3
通讯作者：
Kato, AC
中科院分区：
文献类型：
--
作者：
Sagot, Y;Toni, N;Kato, AC
1细胞凋亡和线粒体功能障碍被认为参与神经退行性疾病的病因学。我们已经在运动神经元变性的动物模型中测试了一种口服活性抗凋亡分子（CGP 3466 B），该分子与甘油醛-3-磷酸脱氢酶（GAPDH）结合，即患有进行性运动神经元病（pmn）的小鼠突变体。2在pmn/pmn小鼠中，在临床症状发作时（出生后2周）口服CGP 3466 B（10-100 nmol kg（-1））。CGP 3466 B减缓了疾病进展，这一点通过寿命延长57%、保持体重和运动性能来确定。3这种改善伴随着运动神经元和运动神经元纤维损失减少以及逆行转运增加。电子显微镜分析显示，CGP 3466 B保护线粒体，线粒体似乎在pmn/pmn小鼠的运动神经元中被选择性破坏。4数据支持评价CGP 3466 B作为运动神经元疾病的潜在治疗。
1 Apoptosis and mitochondrial dysfunction are thought to be involved in the aetiology of neurodegenerative diseases. We have tested an orally active anti-apoptotic molecule (CGP 3466B) that binds to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in an animal model with motoneuron degeneration, i.e. a mouse mutant with progressive motor neuronopathy (pmn).2 In pmn/pmn mice, CGP 3466B was administered orally (10-100 nmol kg(-1)) at the onset of the clinical symptoms (2 weeks after birth). CGP 3466B slowed disease progression as determined by a 57% increase in life-span, preservation of body weight and motor performance.3 This improvement was accompanied by a decreased loss of motoneurons and motoneuron fibres as well as an increase in retrograde transport. Electron microscopic analysis showed that CGP 3466B protects mitochondria which appear to be selectively disrupted in the motoneurons of pmn/pmn mice.4 The data support evaluation of CGP 3466B as a potential treatment for motor neuron disease.