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Nat Rev Drug Discov. 2011 Dec 1;10(12):930-44. doi: 10.1038/nrd3453.

Heat shock transcription factor 1 as a therapeutic target in neurodegenerative diseases.

Author information

1
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina 27710, USA.

Abstract

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and prion-based neurodegeneration are associated with the accumulation of misfolded proteins, resulting in neuronal dysfunction and cell death. However, current treatments for these diseases predominantly address disease symptoms, rather than the underlying protein misfolding and cell death, and are not able to halt or reverse the degenerative process. Studies in cell culture, fruitfly, worm and mouse models of protein misfolding-based neurodegenerative diseases indicate that enhancing the protein-folding capacity of cells, via elevated expression of chaperone proteins, has therapeutic potential. Here, we review advances in strategies to harness the power of the natural cellular protein-folding machinery through pharmacological activation of heat shock transcription factor 1--the master activator of chaperone protein gene expression--to treat neurodegenerative diseases.

PMID:
22129991
PMCID:
PMC3518299
DOI:
10.1038/nrd3453
[Indexed for MEDLINE]
Free PMC Article

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