By targeting the machinery that degrades misfolded proteins, alleviation of Gaucher's disease (GD) can be achieved, as reported in a study published this week in Nature Chemical Biology.
Glucocerebroside ― a lipid found on many cell membranes ― is broken down by the enzyme glucocerebrosidase (GC). In GD, this enzyme is mutated causing it to be misfolded and therefore degraded by the cell's quality control machinery. This leads to glucocerebroside buildup in various organs, such as the kidneys, lung, and brain.
Jeffery Kelly and colleagues find that increasing the levels of cellular calcium with chemical modulators, enhances the function of calnexin, an important part of the protein folding quality control machinery. This allows GC to be properly folded and escape degradation.
Since numerous diseases arise when the quality control machinery recognizes unfolded mutant proteins, single chemical drugs targeting this machinery could be used for treating multiple diseases.