Huntingtin-Encoded Polyglutamine Expansions Form Amyloid-like Protein Aggregates In Vitro and In Vivo
作者： Eberhard Scherzinger , Rudi Lurz , Mark Turmaine , Laura Mangiarini , Birgit Hollenbach
DOI: 10.1016/S0092-8674(00)80514-0
关键词:
摘要: The mechanism by which an elongated polyglutamine sequence causes neurodegeneration in Huntington's disease (HD) is unknown. In this study, we show that the proteolytic cleavage of a GST-huntingtin fusion protein leads to formation insoluble high molecular weight aggregates only when expansion pathogenic range. Electron micrographs these revealed fibrillar or ribbon-like morphology, reminiscent scrapie prions and beta-amyloid fibrils Alzheimer's disease. Subcellular fractionation ultrastructural techniques showed vivo presence structures brains mice transgenic for HD mutation. Our vitro model will aid eventual understanding pathology development preventative strategies.
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