PGC-1α PROTECTS NEURONS AND ALTERS DISEASE PROGRESSION IN AN AMYOTROPHIC LATERAL SCLEROSIS MOUSE MODEL
PGC-1α PROTECTS NEURONS AND ALTERS DISEASE PROGRESSION IN AN AMYOTROPHIC LATERAL SCLEROSIS MOUSE MODEL
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DOI：
10.1002/mus.22217
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发表时间：
2011-12-01
期刊：
影响因子：
3.4
通讯作者：
Van Remmen, Holly
中科院分区：
文献类型：
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作者：
Liang, Huiyun;Ward, Walter F.;Van Remmen, Holly
肌萎缩侧索硬化症（ALS）是一种破坏性的神经退行性疾病。我们试图确定过氧化物酶体增殖物激活受体γ辅激活因子1 α（PGC-1 α）是否对这种疾病有有益的影响。方法：将PGC-1 α转基因小鼠与SOD 1突变型G93 A DL小鼠杂交。结果如下：与G93 A DL小鼠相比，我们观察到PGC-1 alpha/G93 A DL小鼠的平均寿命适度但不显著增加（292 +/-3天vs. 274 +/-7天）。尽管ALS的发作没有改变，但在PGC-1 α/G93 A DL小鼠中，疾病的进展显著较慢（类似于持续时间增加34%）。这些小鼠在转棒测试中也表现出明显改善的表现，并且运动活动的改善与运动神经元的损失减少和神经肌肉接头的退化减少有关。结论：PGC-1 alpha/G93 A DL小鼠星形胶质细胞中持续水平的兴奋性氨基酸转运蛋白2（EAAT 2）可能有助于神经元保护。肌肉神经44：947-956，2011
Introduction: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. We sought to determine whether peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) would have a beneficial effect on this disease. Methods: PGC-1 alpha transgenic mice were crossed with SOD1 mutant G93A DL mice. Results: We observed a moderate but non-significant increase in average lifespan in PGC-1 alpha/G93A DL mice, as compared with G93A DL mice (292 +/- 3 days vs. 274 +/- 7 days). Although the onset of ALS was not altered, progression of the disease was significantly slower (similar to 34% increase in duration) in the PGC-1 alpha/G93A DL mice. These mice also exhibited markedly improved performance on the rotarod test, and the improved motor activity was associated with a decreased loss of motor neurons and less degeneration of neuromuscular junctions. Conclusion: A sustained level of excitatory amino acid transporter protein 2 (EAAT2) in astrocytes of the PGC-1 alpha/G93A DL mice may contribute to neuronal protection. Muscle Nerve 44: 947-956, 2011