Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Mol Neurodegener. 2011 Jul 19;6(1):51. doi: 10.1186/1750-1326-6-51.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects spinal cord and cortical motor neurons. An increasing amount of evidence suggests that mitochondrial dysfunction contributes to motor neuron death in ALS. Peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α) is a principal regulator of mitochondrial biogenesis and oxidative metabolism.
In this study, we examined whether PGC-1α plays a protective role in ALS by using a double transgenic mouse model where PGC-1α is over-expressed in an SOD1 transgenic mouse (TgSOD1-G93A/PGC-1α). Our results indicate that PGC-1α significantly improves motor function and survival of SOD1-G93A mice. The behavioral improvements were accompanied by reduced blood glucose level and by protection of motor neuron loss, restoration of mitochondrial electron transport chain activities and inhibition of stress signaling in the spinal cord.
Our results demonstrate that PGC-1α plays a beneficial role in a mouse model of ALS, suggesting that PGC-1α may be a potential therapeutic target for ALS therapy.
肌萎缩侧索硬化症（ALS）是一种破坏性的神经退行性疾病，影响脊髓和皮质运动神经元。越来越多的证据表明，线粒体功能障碍导致 ALS 中的运动神经元死亡。过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α）是线粒体生物发生和氧化代谢的主要调节因子。
在这项研究中，我们通过使用过表达 PGC-1α的 SOD1 转基因小鼠（TgSOD1-G93A/PGC-1α）的双转基因小鼠模型，研究了 PGC-1α 是否在 ALS 中发挥保护作用。我们的结果表明，PGC-1α 可显著改善 SOD1-G93A 小鼠的运动功能和存活率。行为改善伴随着血糖水平降低以及脊髓中运动神经元丢失、线粒体电子传递链活性恢复和应激信号抑制的保护作用。
我们的结果表明，PGC-1α 在 ALS 小鼠模型中发挥有益作用，表明 PGC-1α 可能是 ALS 治疗的潜在治疗靶点。
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