Huntington's disease (HD) is caused by mutated huntingtin (htt), a toxic protein ubiquitously expressed in nervous and non-nervous system tissues. Fragmentation of htt by caspases and further accumulation in cells of protein aggregates contribute to cell dysfunction and death. In the attempt to elucidate whether this mechanism depends on patients' genotype, we analysed the pattern of htt fragmentation, the caspase 3, 8 and 9 activities and their variation in lymphoblasts with heterozygous and homozygous CAG mutation and in controls. Cells homozygous for expanded mutation showed greater amount of mutated fragments than heterozygotes and controls, caspase 3, 8 and 9 activities greater in mutated than control cell lines, after cyanide treatment, the caspase 3 and 8 particularly increased in homozygotes. This data offers a biological explanation to the clinical in-patients evidence of mutation homozygosity associated with more severe phenotype

Huntingtin fragmentation and increased caspase 3, 8 and 9 activities in lymphoblasts with heterozygous and homozygous Huntington's disease mutation / MAGLIONE V., CANNELLA M; Gradini, Roberto; Cislaghi, G; Russo, Matteo Antonio; Squitieri, F.. - In: MECHANISMS OF AGEING AND DEVELOPMENT. - ISSN 0047-6374. - 127(2):(2006), pp. 213-216. [10.1016/j.mad.2005.09.011]

Huntingtin fragmentation and increased caspase 3, 8 and 9 activities in lymphoblasts with heterozygous and homozygous Huntington's disease mutation.

GRADINI, Roberto;RUSSO, Matteo Antonio;
2006

Abstract

Huntington's disease (HD) is caused by mutated huntingtin (htt), a toxic protein ubiquitously expressed in nervous and non-nervous system tissues. Fragmentation of htt by caspases and further accumulation in cells of protein aggregates contribute to cell dysfunction and death. In the attempt to elucidate whether this mechanism depends on patients' genotype, we analysed the pattern of htt fragmentation, the caspase 3, 8 and 9 activities and their variation in lymphoblasts with heterozygous and homozygous CAG mutation and in controls. Cells homozygous for expanded mutation showed greater amount of mutated fragments than heterozygotes and controls, caspase 3, 8 and 9 activities greater in mutated than control cell lines, after cyanide treatment, the caspase 3 and 8 particularly increased in homozygotes. This data offers a biological explanation to the clinical in-patients evidence of mutation homozygosity associated with more severe phenotype
2006
01 Pubblicazione su rivista::01a Articolo in rivista
Huntingtin fragmentation and increased caspase 3, 8 and 9 activities in lymphoblasts with heterozygous and homozygous Huntington's disease mutation / MAGLIONE V., CANNELLA M; Gradini, Roberto; Cislaghi, G; Russo, Matteo Antonio; Squitieri, F.. - In: MECHANISMS OF AGEING AND DEVELOPMENT. - ISSN 0047-6374. - 127(2):(2006), pp. 213-216. [10.1016/j.mad.2005.09.011]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/114809
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