Broadening the therapeutic scope for rapamycin treatment.
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.
Menzies
Fiona M
FM
Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, UK.
Rubinsztein
David C
DC
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000067699:Ataxin-3; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000473:pathology; D017827:Machado-Joseph Disease / Q000188:drug therapy / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C401859:temsirolimus; C092341:ATXN3 protein, human; D000067699:Ataxin-3; D020123:Sirolimus