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.
Original language | English |
---|---|
Pages (from-to) | 1307-15 |
Number of pages | 9 |
Journal | Human Molecular Genetics |
Volume | 10 |
Issue number | 12 |
Publication status | Published - 1 Jun 2001 |
Keywords
- Amino Acid Sequence
- Animals
- Benzoquinones
- COS Cells
- Exons
- HSP40 Heat-Shock Proteins
- HSP70 Heat-Shock Proteins
- HSP90 Heat-Shock Proteins
- Heat-Shock Proteins
- Heat-Shock Response
- Huntingtin Protein
- Huntington Disease
- Lactams, Macrocyclic
- Molecular Sequence Data
- Mutation
- Nerve Tissue Proteins
- Nuclear Proteins
- Peptides
- Quinones
- Journal Article
- Research Support, Non-U.S. Gov't