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The hypothesis that htt proteolysis represents a critical step in Huntington disease (HD) pathogenesis was first suggested in 1996 when htt was identified as a substrate for caspase-3. Indeed, htt was the first caspase substrate to be identified in the brain. Since that time, the identification of caspase-generated N-terminal htt fragments in the patient brain and the accelerated phenotype of transgenic...
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