Glucocerebrosidase Targeting Therapies Study

As a leader in neuroscience, Creative Biolabs is committed to providing comprehensive services to customers around the world, from the establishment of Parkinson's disease (PD) animal models to the evaluation of the efficacy of target molecules in PD. Highly predictive disease models and extensive experience make Creative Biolabs the best choice for your Glucosylceramidase (GCase) targeting therapies study.

Overview of Glucocerebrosidase

GCase is a 497 amino acid lysosomal enzyme encoded by the GBA gene. GCase is an enzyme involved in sphingolipid metabolism, which plays a crucial role in the hydrolysis of glucosylceramide to ceramide and glucose. Mutations in GBA severely affect GCase activity and promote the accumulation of its substrates in lysosomes, leading to autosomal recessive Gaucher disease (GD). Individuals with GBA pathogenic variants, which are the most prevalent genetic factor of PD, are at increased risk for dementia. What's more, mutations in the GBA gene occur in approximately 8% of PD patients.

GBA and PD

PD is considered to be a multifactorial central system disease that is typically characterized by the decline of dopaminergic neurons as well as the aggregation of α-synuclein. For decades, the pathogenesis of PD has been the focus of many studies aimed at finding effective treatment strategies. Available evidence suggests that GCases can affect α-synuclein pathology in different ways. For example, lack of GCase leads to the agglomeration of substrates, which in turn binds to α-synuclein and promotes the pathological formation of aggregates. Furthermore, α-synuclein can reduce the enzymatic activity of GCase, suggesting a bidirectional interaction between GCase and α-synuclein. It is worth noting that GCase activity is significantly reduced in PD brains with heterozygous GBA mutations, especially in the substantia nigra.

Fig.1 The pathogenesis of GCase mutations in PD. (Beavan, 2013)

GCase Targeting Therapies Study

In-depth exploration of GBA, especially increasing the level of GCase, offers new therapeutic perspectives for coping with PD. Given the interconnectedness between GCase and α-synuclein, GCase is considered to be a promising therapeutic target. Indeed, modulation of GCase is an attractive approach for the therapy of PD with GBA mutations and other forms of PD with reduced GCase activity. Small chaperones capable of crossing the blood-brain barrier and increasing GCase activity in neurons have been one of these new strategies. More importantly, several drug screens have identified some novel molecular chaperones that have been shown to increase GCase activity in neurons.

With our advanced platform and professional team, we focus on providing you with customized services to help you gain a deep understanding of the mechanism of PD. Please contact us in time to discuss your plans for professional advice.

Reference

1. Beavan, M. S.; Schapira, A. H. Glucocerebrosidase mutations and the pathogenesis of Parkinson's disease. Annals of medicine. 2013, 45(8): 511-521.