Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Muscle Nerve. 2011 Dec;44(6):947-56. doi: 10.1002/mus.22217.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. We sought to determine whether peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) would have a beneficial effect on this disease.
PGC-1α transgenic mice were crossed with SOD1 mutant G93A DL mice.
We observed a moderate but non-significant increase in average lifespan in PGC-1α/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 (≈34% increase in duration) in the PGC-1α/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.
A sustained level of excitatory amino acid transporter protein 2 (EAAT2) in astrocytes of the PGC-1α/G93A DL mice may contribute to neuronal protection.
肌萎缩侧索硬化症（ALS）是一种毁灭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共激活因子 1α（PGC-1α）是否对这种疾病有有益的影响。
将 PGC-1α 转基因小鼠与 SOD1 突变 G93A DL 小鼠杂交。
与 G93A DL 小鼠相比，我们观察到 PGC-1α/G93A DL 小鼠的平均寿命有适度但无统计学意义的延长（292±3 天 vs. 274±7 天）。虽然 ALS 的发病没有改变，但 PGC-1α/G93A DL 小鼠的疾病进展明显较慢（持续时间延长约 34%）。这些小鼠在旋转棒试验中的表现也明显改善，运动活动的改善与运动神经元的减少和运动神经元减少相关神经肌肉接头的退化。
PGC-1α/G93A DL 小鼠星形胶质细胞中兴奋性氨基酸转运蛋白 2（EAAT2）的持续水平可能有助于神经元保护。
