The Gpx4NIKO Mouse Is a Versatile Model for Testing Interventions Targeting Ferroptotic Cell Death of Spinal Motor Neurons.
The Gpx4NIKO Mouse Is a Versatile Model for Testing Interventions Targeting Ferroptotic Cell Death of Spinal Motor Neurons.
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DOI：
10.1007/s12640-021-00469-0
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发表时间：
2022-04
影响因子：
3.7
通讯作者：
Ran, Qitao
中科院分区：
文献类型：
--
作者：
Evans, Robert Cole;Chen, Liuji;Na, Ren;Yoo, Kwangsun;Ran, Qitao
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The degeneration and death of motor neurons leads to motor neuron diseases such as Amyotrophic Lateral Sclerosis (ALS). Although the exact mechanism by which motor neuron degeneration occurs is not well understood, emerging evidence implicates the involvement of ferroptosis, an iron-dependent oxidative mode of cell death. We reported previously that treating Gpx4NIKO mice with tamoxifen to ablate the ferroptosis regulator glutathione peroxidase 4 (GPX4) in neurons produces a severe paralytic model resembling an accelerated form of ALS that appears to be caused by ferroptotic cell death of spinal motor neurons. In this study, in support of the role of ferroptosis in this model, we found that the paralytic symptoms and spinal motor neuron death of Gpx4NIKO mice was attenuated by a chemical inhibitor of ferroptosis. In addition, we observed that the paralytic symptoms of Gpx4NIKO mice were malleable and could be tapered by lowering the dose of tamoxifen, allowing for the generation of a mild paralytic model without a rapid onset of death. We further used both models to evaluate mitochondrial reactive oxygen species (mtROS) in the ferroptosis of spinal motor neurons and showed that overexpression of peroxiredoxin 3, a mitochondrial antioxidant defense enzyme, ameliorated symptoms of the mild but not the severe model of the Gpx4NIKO mice. Our results thus indicate that the Gpx4NIKO mouse is a versatile model for testing interventions that target ferroptotic death of spinal motor neurons in vivo.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
19
作者：
Yang WS;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
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作者：
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通讯作者：
Butterfield, DA
影响因子：
3.9
作者：
Drey, M.;Groesch, C.;Sieber, C. C.
通讯作者：
Sieber, C. C.
DOI：
10.1073/pnas.1415518111
发表时间：
2014-11-25
影响因子：
11.1
作者：
Linkermann, Andreas;Skouta, Rachid;Krautwald, Stefan
通讯作者：
Krautwald, Stefan