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CONy 2023 | Glucoceribrosidase as a target for intervention in PD

Tiago Outeiro, PhD, University Medical Center Göttingen, Göttingen, Germany, discusses glucocerebrosidase (GCase) as a target for intervention in Parkinson’s disease (PD). Since the link between Gaucher disease patients and parkinsonism was established, it is recognized that deficient GCase has some biological role as a modifier or facilitator of PD pathogenesis. Therefore, strategies targeting GCase started to be investigated for treating PD, including a clinical trial of a molecule to limit the accumulation of the substrate processed by the enzyme. Unfortunately, that trial was stopped, but other strategies are being studied nowadays, such as those looking at increasing the activity of GCase. It is thought that increasing the activity of this enzyme will help cells process α-synuclein, a protein known to be involved in PD pathogenesis. Although the current understanding of the GCase pathway suggests that increasing the enzymatic activity might be the most beneficial modulation, strategies to decrease the enzymatic activity should also be considered. This interview took place at the 17th World Congress on Controversies in Neurology (CONy) in Dubrovnik, Croatia.

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