Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease
Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease
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DOI：
10.1038/77528
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发表时间：
2000-07-01
期刊：
影响因子：
82.9
通讯作者：
Friedlander, RM
中科院分区：
文献类型：
--
作者：
Chen, M;Ona, VO;Friedlander, RM
亨廷顿疾病是一种常染色体显性神经退行性疾病，没有有效的治疗。 Minocycline是具有可靠安全性的四环素衍生物。缺血后，米诺环素抑制caspase-1和诱导的一氧化氮合成酶上调，并减少梗塞。由于caspase-1和一氧化氮似乎在亨廷顿疾病中起作用，因此我们评估了在亨廷顿疾病的R6/2小鼠模型中米诺环素的治疗功效。我们报告说，米诺环素会延迟疾病的进展，抑制caspase-1和caspase-3 mRNA上调，并降低诱导型一氧化氮合成酶活性。此外，R6/2小鼠的有效药物疗法需要caspase-1和caspase-3抑制作用。这是亨廷顿疾病模型中caspase-1和caspase-3转录调控的首次演示。
Huntington disease is an autosomal dominant neurodegenerative disease with no effective treatment. Minocycline is a tetracycline derivative with proven safety. After ischemia, minocycline inhibits caspase-1 and inducible nitric oxide synthetase upregulation, and reduces infarction. As caspase-1 and nitric oxide seem to play a role in Huntington disease, we evaluated the therapeutic efficacy of minocycline in the R6/2 mouse model of Huntington disease. We report that minocycline delays disease progression, inhibits caspase-1 and caspase-3 mRNA upregulation, and decreases inducible nitric oxide synthetase activity. In addition, effective pharmacotherapy in R6/2 mice requires caspase-1 and caspase-3 inhibition. This is the first demonstration of caspase-1 and caspase-3 transcriptional regulation in a Huntington disease model.