| First Author | Ona VO | Year | 1999 |
| Journal | Nature | Volume | 399 |
| Issue | 6733 | Pages | 263-7 |
| PubMed ID | 10353249 | Mgi Jnum | J:55036 |
| Mgi Id | MGI:1337161 | Doi | 10.1038/20446 |
| Citation | Ona VO, et al. (1999) Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease [see comments]. Nature 399(6733):263-7 |
| abstractText | Huntington's disease is an autosomal-dominant progressive neurodegenerative disorder resulting in specific neuronal loss and dysfunction in the striatum and cortex(1). The disease is universally fatal, with a mean survival following onset of 15-20 years and, at present, there is no effective treatment. The mutation in patients with Huntington's disease is an expanded CAG/polyglutamine repeat in huntingtin, a protein of unknown function with a relative molecular mass of 350,000 (M-r 350K)(2). The length of the CAG/polyglutamine repeat is inversely correlated with the age of disease onset. The molecular pathways mediating the neuropathology of Huntington's disease are poorly understood. Transgenic mice expressing exon 1 of the human huntingtin gene with an expanded CAG/ polyglutamine repeat develop a progressive syndrome with many of the characteristics of human Huntington's disease(3). Here we demonstrate evidence of caspase-1 activation in the brains of mice and humans with the disease. In this transgenic mouse model of Huntington's disease, expression of a dominant-negative caspase-1 mutant extends survival and delays the appearance of neuronal inclusions, neurotransmitter receptor alterations and onset of symptoms, indicating that caspase-1 is important in the pathogenesis of the disease. In addition, we demonstrate that intracerebroventricular administration of a caspase inhibitor delays disease progression and mortality in the mouse model of Huntington's disease. |
