Spinobulbar muscular atrophy (SBMA) is caused by an expansion of a CAG repeat in the androgen receptor (AR), resulting in a polyglutamine tract in the AR. Wang et al. showed that overexpression of heat shock protein 70 (HSP70)-interacting protein (HIP), a chaperone that promotes binding of HSP70 to its substrates, promoted the clearance of polyglutamine AR in vitro. They identified a compound that acted similarly to HIP (by allosterically promoting HSP70 binding to unfolded substrates) and reduced toxicity in a fruitfly model of SBMA.
ORIGINAL RESEARCH PAPER
Wang, A. M. et al. Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation. Nature Chem. Biol. 9 Dec 2012 (doi:10.1038/nchembio.1140)
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Harrison, C. Reducing androgen receptor-mediated toxicity. Nat Rev Drug Discov 12, 102 (2013). https://doi.org/10.1038/nrd3951
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DOI: https://doi.org/10.1038/nrd3951
