Fundamental studies on the biochemical mechanism of chemical chaperoning of glucocerebrosidase

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Parkinson's disease is a worldwide health problem that has been linked to deficiencies in an enzyme called glucocerebrosidase. This enzyme plays a critical role in the body by breaking down a particular large molecule into two smaller, more easily metabolized components, a sugar (glucose) and a fat (ceramide). Without a properly functioning glucocerebrosidase, these large molecules are not degraded in a normal manner. Genetic mutations associated with glucocerebrosidase often result in an unstable enzyme structure that is easily damaged in the intracellular environment. In the case of Parkinson's disease, loss of function of this enzyme may contribute to disease progression. Current treatments for Parkinson's disease address disease symptoms but do not affect disease progression. New disease-modifying therapies are therefore urgently required. The collaboration between Alectos Therapeutics and the Bennet group at Simon Fraser University will address basic scientific questions around the finely tuned activities that enable this important enzyme to function properly. The project will be guided by the Bennet group's ingenuity in the area of enzyme biochemistry and will provide unique opportunities for these university researchers to work alongside industry scientists at Alectos Therapeutics. Anticipated scientific advances made by this university - industry partnership include the design of small molecules that strengthen the enzyme's structure, helping to increase its robustness and hence its ability to function properly. Not only will this work broaden our understanding of the molecular details inherent in enzyme function, but this knowledge will also drive the downstream design of new strategies to prevent and treat Parkinson's disease.