caa a22 4500 397573383 CHVBK 20180308164847.0 cr unu---uuuuu 161202e199609 xx s 000 0 eng 10.1093/hmg/5.Supplement_1.1431 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.Supplement_1.1431 Huntington disease: new insights into the relationship between CAG expansion and disease [Elektronische Daten] [Jamal Nasir, Y. Paul Goldberg, Michael R. Hayden] The mutation underlying Huntington disease (HD) is CAG expansion beyond 35 repeats within a novel gene. Recently, new insights into the role of the HD protein (huntingtin) in the pathogenesis of HD have emerged. The CAG is translated and expression of mutant huntingtin is essential for neuronal death. Huntingtin is crucial for normal development and may be regarded as a cell survival gene. Huntingtin is specifically cleaved during apoptosis by a key cysteine protease, apopain, known to play a pivotal role in apoptotic cell death. The rate of cleavage is enhanced by longer polyglutamine tracts, suggesting that inappropriate apoptosis underlies HD. Recently, three proteins have been identified and have been shown specifically to interact with huntingtin, two of these interactions being influenced by CAG length. Several different approaches to develop an animal model for HD include cDNA and YAC transgenics, as well as ‘knock-in' strategies. Such a model will be critical for the understanding of the natural history of HD and for the testing of new therapeutic modalities. © 1996 Oxford University Press Nasir Jamal Department of Medical Genetics and the Centre for Molecular Medicine and Therapeutics, University of British Columbia, 416-2125 East Mall, NCE Building, Vancouver, BC, V6T 1Z4, Canada aut Goldberg Y. Paul Department of Medical Genetics and the Centre for Molecular Medicine and Therapeutics, University of British Columbia, 416-2125 East Mall, NCE Building, Vancouver, BC, V6T 1Z4, Canada aut Hayden Michael R. Department of Medical Genetics and the Centre for Molecular Medicine and Therapeutics, University of British Columbia, 416-2125 East Mall, NCE Building, Vancouver, BC, V6T 1Z4, Canada aut Human Molecular Genetics Oxford University Press 5/Supplement_1(1996-09), 1431-1435 0964-6906 5:Supplement_1<1431 1996 5 hmg https://doi.org/10.1093/hmg/5.Supplement_1.1431 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.Supplement_1.1431 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nasir Jamal Department of Medical Genetics and the Centre for Molecular Medicine and Therapeutics, University of British Columbia, 416-2125 East Mall, NCE Building, Vancouver, BC, V6T 1Z4, Canada aut NATIONALLICENCE 700 1- Goldberg Y. Paul Department of Medical Genetics and the Centre for Molecular Medicine and Therapeutics, University of British Columbia, 416-2125 East Mall, NCE Building, Vancouver, BC, V6T 1Z4, Canada aut NATIONALLICENCE 700 1- Hayden Michael R. Department of Medical Genetics and the Centre for Molecular Medicine and Therapeutics, University of British Columbia, 416-2125 East Mall, NCE Building, Vancouver, BC, V6T 1Z4, Canada aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/Supplement_1(1996-09), 1431-1435 0964-6906 5:Supplement_1<1431 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford