Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease.

M Chen, V O Ona, M Li, R J Ferrante, K B Fink, S Zhu, J Bian, L Guo, L A Farrell, S M Hersch, W Hobbs, J P Vonsattel, J H Cha, R M Friedlander

Neuroapoptosis Laboratory, Neurosurgical Service, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

Nature medicine 2000 Jul

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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.

Citation

M Chen, V O Ona, M Li, R J Ferrante, K B Fink, S Zhu, J Bian, L Guo, L A Farrell, S M Hersch, W Hobbs, J P Vonsattel, J H Cha, R M Friedlander. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nature medicine. 2000 Jul;6(7):797-801