D.C. Rubinsztein

The deposition of protein aggregates in specific target organs is a feature of many human diseases referred to as Protein Conformation Disorders (PCD). These include Alzheimer's disease, Parkinson's disease, Huntington's disease (HD) and Oculopharyngeal muscular dystrophy (OPMD). The role of aggregates in these diseases has been a subject of vigorous debate. However, irrespective of the nature(s) of the toxic species, it is desirable for cells to be able to control the levels of these toxic proteins and restrict their accumulation. Macroautophagy (which I will call autophagy) is involved in the clearance of mutant huntingtin in cell models, in flies and in mouse models of disease. Mutations that impede autophagy enhance the toxicity of this mutant protein. Activation of autophagy with rapamycin prior to disease onset reduces the levels of the mutant protein, resulting in decreased aggregate formation and attenuated toxicity/delayed onset. Our data suggest that these protective effects are not confined to mutant huntingtin but may be relevant to certain other PCDs in vivo.

Keywords (Optional): 
Huntington's disease