Caspase-11 mediates inflammatory dopaminergic cell death in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease
Caspase-11 mediates inflammatory dopaminergic cell death in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease
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DOI：
10.1523/jneurosci.3309-03.2004
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发表时间：
2004-02-25
影响因子：
5.3
通讯作者：
Mochizuki, H
中科院分区：
文献类型：
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作者：
Furuya, T;Hayakawa, H;Mochizuki, H
本研究旨在阐明1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的帕金森病模型神经毒性的炎症和凋亡机制。我们的研究结果表明，缺乏caspase-11基因的突变小鼠比野生型小鼠对MPTP急性治疗的抵抗力更强。因此，MPTP的神经毒性似乎是通过诱导线粒体功能障碍和自由基产生介导的。以前，我们发现Apaf-1显性负性抑制剂的过度表达在慢性MPTP治疗中抑制了线粒体凋亡级联反应，但在急性MPTP治疗中没有。目前的研究结果表明，MPTP的神经毒性可能是通过激活caspase-11级联和炎症级联，以及线粒体凋亡级联介导的。
The present study was designed to elucidate the inflammatory and apoptotic mechanisms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ( MPTP)-induced neurotoxicity in a model of Parkinson's disease. Our results showed that mutant mice lacking the caspase-11 gene were significantly more resistant to the effects of acute treatment with MPTP than their wild-type mice. Thus, the neurotoxicity of MPTP seems to be mediated by the induction of both mitochondrial dysfunction and free radical generation. Previously, we showed that overexpression of the Apaf-1 dominant-negative inhibitor inhibited the mitochondrial apoptotic cascade in chronic MPTP treatment but not in acute MPTP treatment. The present results indicate that MPTP neurotoxicity may be mediated via activation of the caspase-11 cascade and inflammatory cascade, as well as the mitochondrial apoptotic cascade.