Caspase Cleavage of Mutant Huntingtin Precedes Neurodegeneration in Huntington's Disease

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Fig. 7.
Fig. 7.

Kinetic analysis of htt cleavage in brain homogenates. A, YAC72 (high expressing) whole-brain homogenate prepared in the absence of zVAD-fmk was incubated for various times with a final concentration of 2 nm caspase-3, followed by immunodetection of cleavage fragments with BKP1. Over time, total intact htt (Intact) is converted to four major cleavage products, including mutant transgenic htt cleaved at amino acid 552 (Mut-552), mutant transgenic htt cleaved at amino acid 513 (Mut-513), wild-type endogenous htt cleaved at amino acid 552 (WT-552), and wild-type endogenous htt cleaved at amino acid 513 (WT-513).B, Quantitation of the percentage of reduction of intact total htt and percentage of accumulation of each of the htt cleavage products shows that mutant and wild-type cleavage products accumulate at equivalent rates.

  1. The Journal of Neuroscience vol. 22 no. 18 7862-7872
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