[HTML][HTML] Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells
CL Wellington, L Ellerby, J Savill, S Roy… - Journal of Biological …, 2000 - ASBMB
Huntington's disease is a neurodegenerative disorder caused by CAG expansion that
results in expansion of a polyglutamine tract at the extreme N terminus of huntingtin (htt). htt
with polyglutamine expansion is proapoptotic in different cell types. Here, we show that
caspase inhibitors diminish the toxicity of htt. Additionally, we define htt itself as an important
caspase substrate by generating a site-directed htt mutant that is resistant to caspase-3
cleavage at positions 513 and 530 and to caspase-6 cleavage at position 586. In contrast to …
results in expansion of a polyglutamine tract at the extreme N terminus of huntingtin (htt). htt
with polyglutamine expansion is proapoptotic in different cell types. Here, we show that
caspase inhibitors diminish the toxicity of htt. Additionally, we define htt itself as an important
caspase substrate by generating a site-directed htt mutant that is resistant to caspase-3
cleavage at positions 513 and 530 and to caspase-6 cleavage at position 586. In contrast to …
