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- W2194480672 abstract "Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by a polyglutamine expansion in the androgen receptor (AR) and is associated with misfolding and aggregation of the mutant AR. We investigated the role of an interdomain interaction between the amino (N)-terminal FxxLF motif and carboxyl (C)-terminal AF-2 domain in a mouse model of SBMA. Male transgenic mice expressing polyQ-expanded AR with a mutation in the FxxLF motif (F23A) to prevent the N/C interaction displayed substantially improved motor function compared with N/C-intact AR-expressing mice and showed reduced pathological features of SBMA. Serine 16 phosphorylation was substantially enhanced by the F23A mutation; moreover, the protective effect of AR F23A was dependent on this phosphorylation. These results reveal an important role for the N/C interaction on disease onset in mice and suggest that targeting AR conformation could be a therapeutic strategy for patients with SBMA." @default.
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- W2194480672 date "2015-12-01" @default.
- W2194480672 modified "2023-10-10" @default.
- W2194480672 title "Preventing the Androgen Receptor N/C Interaction Delays Disease Onset in a Mouse Model of SBMA" @default.
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- W2194480672 doi "https://doi.org/10.1016/j.celrep.2015.11.019" @default.
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