Cheryl L Wellington, Lisa M Ellerby, Claire-Anne Gutekunst, Danny Rogers, Simon Warby, Rona K Graham, Odell Loubser, Jeremy van Raamsdonk, Roshni Singaraja, Yu-Zhou Yang, Juliette Gafni, Dale Bredesen, Steven M Hersch, Blair R Leavitt, Sophie Roy, Donald W Nicholson, Michael R Hayden
Huntington's disease (HD) results from polyglutamine expansion in huntingtin (htt), a protein with several consensus caspase cleavage sites. Despite the identification of htt fragments in the brain, it has not been shown conclusively that htt is cleaved by caspases in vivo. Furthermore, no study has addressed when htt cleavage occurs with respect to the onset of neurodegeneration. Using antibodies that detect only caspase-cleaved htt, we demonstrate that htt is cleaved in vivo specifically at the caspase consensus site at amino acid 552...
September 15, 2002: Journal of Neuroscience