Access
To read this story in full you will need to login or make a payment (see right).
Article
Nature Medicine 13, 348 - 353 (2007)
Published online: 4 March 2007 | doi:10.1038/nm1547
ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor
Zhiming Yang1,2,7, Yu-Jia Chang1,3,7, I-Chen Yu1, Shuyuan Yeh1, Cheng-Chia Wu1,3, Hiroshi Miyamoto1, Diane E Merry4, Gen Sobue5, Lu-Min Chen1,6, Shu-Shi Chang1,6 & Chawnshang Chang1
Abstract
Motor neuron degeneration resulting from the aggregation of the androgen receptor with an expanded polyglutamine tract (AR-polyQ) has been linked to the development of spinal and bulbar muscular atrophy (SBMA or Kennedy disease). Here we report that adding 5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)-1,4,6-heptatrien-3-one (ASC-J9) disrupts the interaction between AR and its coregulators, and also increases cell survival by decreasing AR-polyQ nuclear aggregation and increasing AR-polyQ degradation in cultured cells. Intraperitoneal injection of ASC-J9 into AR-polyQ transgenic SBMA mice markedly improved disease symptoms, as seen by a reduction in muscular atrophy. Notably, unlike previous approaches in which surgical or chemical castration was used to reduce SBMA symptoms, ASC-J9 treatment ameliorated SBMA symptoms by decreasing AR-97Q aggregation and increasing VEGF164 expression with little change of serum testosterone. Moreover, mice treated with ASC-J9 retained normal sexual function and fertility. Collectively, our results point to a better therapeutic and preventative approach to treating SBMA, by disrupting the interaction between AR and AR coregulators.
To read this story in full you will need to login or make a payment (see right).
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptorNature Medicine Article
ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptorNature Medicine Article (01 Mar 2007)
Leuprorelin rescues polyglutamine-dependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophyNature Medicine Article (01 Jun 2003)
See all 12 matches for Research