Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease
Open Access
- 1 June 2001
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 10 (12) , 1307-1315
- https://doi.org/10.1093/hmg/10.12.1307
Abstract
Huntington’s disease (HD) is a progressive neurodegenerative disorder with no effective treatment. Geldanamycin is a benzoquinone ansamycin that binds to the heat shock protein Hsp90 and activates a heat shock response in mammalian cells. In this study, we show by using a filter retardation assay and immunofluorescence microscopy that treatment of mammalian cells with geldanamycin at nanomolar concentrations induces the expression of Hsp40, Hsp70 and Hsp90 and inhibits HD exon 1 protein aggregation in a dose-dependent manner. Similar results were obtained by overexpression of Hsp70 and Hsp40 in a separate cell culture model of HD. This is the first demonstration that huntingtin protein aggregation in cells can be suppressed by chemical compounds activating a specific heat shock response. These findings may provide the basis for the development of a novel pharmacotherapy for HD and related glutamine repeat disorders.Keywords
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