Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington’s disease
作者： Annie Sittler , Rudi Lurz , Gerhild Lueder , Josef Priller , Manajit K Hayer-Hartl
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摘要: Huntington's disease (HD) is a progressive neurodegenerative disorder with no effective treatment. Geldanamycin benzoquinone ansamycin that binds to the heat shock protein Hsp90 and activates response in mammalian cells. In this study, we show by using filter retardation assay immunofluorescence microscopy treatment of cells geldanamycin at nanomolar concentrations induces expression Hsp40, Hsp70 inhibits HD exon 1 aggregation dose-dependent manner. Similar results were obtained overexpression Hsp40 separate cell culture model HD. This first demonstration huntingtin can be suppressed chemical compounds activating specific response. These findings may provide basis for development novel pharmacotherapy related glutamine repeat disorders.
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