Fundamental studies on the biochemical mechanism of chemical chaperoning of glucocerebrosidase

葡萄糖脑苷脂酶化学伴侣生化机制的基础研究

• 批准号: 480335-2015
• 负责人: Bennet, Andrew
• 金额: $ 5.1万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=580750
• 关键词: Fundamental; studies; biochemical; mechanism; chemical

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.

帕金森氏病是一个全球健康问题，与一种称为葡萄糖脑溴糖苷酶的酶中的缺陷有关。通过将特定的大分子分解为两个较小，更容易代谢的成分，糖（葡萄糖）和脂肪（ceramide），这种酶在体内起关键作用。如果没有正确运行的葡萄糖脑苷酶，这些大分子不会以正常方式降解。与葡萄糖脑苷酶相关的遗传突变通常会导致不稳定的酶结构，在细胞内环境中很容易受损。 在帕金森氏病的情况下，该酶的功能损失可能导致疾病进展。 当前对帕金森氏病的治疗方法解决了疾病症状，但不会影响疾病的进展。因此，迫切需要新的改良疾病改良疗法。 Simon Fraser University的Alectos Therapeutics与Bennet Group之间的合作将解决围绕精心调整的活动的基本科学问题，从而使该重要酶能够正常运行。该项目将由Bennet Group在酶生物化学领域的创造力进行指导，并将为这些大学研究人员与Alectos Therapeutics的行业科学家一起工作提供独特的机会。这所大学的预期科学进步 - 行业伙伴关系包括设计酶结构的小分子的设计，有助于提高其稳健性，从而使其正常运作的能力。这项工作不仅会扩大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预防和治疗帕金森氏病的新策略的下游设计。