. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell. 2006 Jun 16;125(6):1179-91. PubMed.

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  1. Pat McCaffrey's coverage of this paper is excellent. The only thing I have to add is that it is unlikely that the active caspase, be it caspase-6 or another caspase, is selective for one protein.

    Therefore, identifying the insult activating the caspase in neurodegenerative diseases, or finding neuron-specific caspase inhibitors, is probably the best chance we have at inhibiting these pathways. The downstream events will be too numerous to control. It is nevertheless interesting that in the Huntington mouse model and in Bredesen's APP transgene that the generation of that one huntingtin or APP fragment is sufficient to induce neurodegeneration.

    View all comments by Andrea LeBlanc