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Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease
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Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease
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Journal Article
Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease
2000
Overview
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Anti-Bacterial Agents - therapeutic use
/ Biomedical and Life Sciences
/ Enzyme Activation - drug effects
/ Glucose
/ Huntington Disease - drug therapy
/ Huntington Disease - mortality
/ interleukin 1^b-converting enzyme
/ interleukin 1b-converting enzyme
/ Ischemia
/ Medicine
/ Mice
/ Minocycline - therapeutic use
/ Neuroprotective Agents - therapeutic use
/ Nitric Oxide Synthase - drug effects
