Fundamental studies on the biochemical mechanism of chemical chaperoning of glucocerebrosidase

帕金森氏症是一个世界性的健康问题，它与一种名为葡萄糖脑苷酶的酶的缺乏有关。这种酶通过将特定的大分子分解成两个更小、更容易代谢的成分--糖(葡萄糖)和脂肪(神经酰胺)--在人体内发挥关键作用。如果没有功能正常的葡萄糖脑苷酶，这些大分子就不会以正常方式降解。与葡萄糖脑苷酶相关的基因突变通常会导致一种不稳定的酶结构，在细胞内环境中容易受到破坏。在帕金森氏症的病例中，这种酶功能的丧失可能导致疾病的进展。 目前帕金森氏症的治疗方法针对的是疾病症状，但并不影响疾病的进展。因此，迫切需要新的治疗疾病的方法。阿莱克托斯治疗公司和西蒙弗雷泽大学的Bennet小组之间的合作将解决围绕使这种重要酶正常发挥作用的微调活动的基本科学问题。该项目将由Bennet集团在酶生物化学领域的独创性指导，并将为这些大学研究人员提供独特的机会，与Alectos治疗公司的行业科学家合作。这一大学-行业合作伙伴关系预期取得的科学进展包括设计加强酶结构的小分子，帮助增加其稳定性，从而提高其正常运作的能力。这项工作不仅将拓宽我们对酶功能固有的分子细节的理解，而且这些知识还将推动下游预防和治疗帕金森氏症的新策略的设计。

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.