Candidate molecules for chemical chaperone therapy of GM1-gangliosidosis.

A growing body of evidence suggests that misfolding of a mutant protein followed by its aggregation or premature degradation in the endoplasmic reticulum is one of the main mechanisms that underlie inherited neurodegenerative diseases, including lysosomal storage diseases. Chemical or pharmacological chaperones are small molecules that bind to and stabilize mutant lysosomal enzyme proteins in the endoplasmic reticulum. A number of chaperone compounds for lysosomal hydrolases have been identified in the last decade. They have gained attention because they can be orally administrated, and also because they can penetrate the blood-brain barrier. In this article, we describe two chaperone candidates for the treatment of GM1-gangliosidosis. We also discuss the future direction of this strategy targeting other lysosomal storage diseases as well as protein misfolding diseases in general.