Broadening the therapeutic scope for rapamycin treatment

被引:23
作者
Menzies, Fiona M. [1 ]
Rubinsztein, David C. [1 ]
机构
[1] Univ Cambridge, Addenbrookes Hosp, Dept Med Genet, Cambridge Inst Med Res, Cambridge CB2 2QQ, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
autophagy; rapamycin; mTOR; polyglutamine disease; spinocerebellar ataxia type 3; Machado-Joseph disease;
D O I
10.4161/auto.6.2.11078
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The role of autophagy in the degradation of aggregate-prone proteins has been well established. As a result, autophagy upregulation has become an attractive therapeutic strategy for the treatment of proteinopathies, a group of diseases caused by the accumulation of mutant misfolded proteins. We have previously shown that rapamycin attenuates the phenotype in a mouse model of Huntington disease when administered pre-symptomatically and have recently extended this to demonstrate the effectiveness of rapamycin in a transgenic mouse model of spinocerebellar ataxia type 3, a polyglutamine disorder caused by mutations in the ataxin-3 gene. Rapamycin, administered from the initial onset of disease signs, improves motor coordination and results in a decrease in the levels of soluble mutant ataxin-3 and protein aggregates in the brain.
引用
收藏
页码:286 / +
页数:2
相关论文
empty
未找到相关数据