Topic: glucocerebrosidase

Dopaminergic neuron cell death in Parkinson’s Disease (PD) is complex and combinatorial, with impairments in multiple cellular pathways impacting mitochondrial function, endosomal/lysosomal protein degradation, alpha-synuclein and tau aggregation, and neuroinflammation. Genetic risk factors, such as mutations in leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GBA), have been shown to impact kinetics of the autophagiclysosomal pathway (ALP), which is suggested to contribute to PD-associated protein accumulation and aggregation. Human-relevant in vitro models using patient-derived i

Gaucher’s disease (GD) is a genetic disorder characterized by loss of glucocerebrosidase activity in cells resulting in accumulation of glucocerebroside. Mutation of GBA1, which encodes the lysosomal glucocerebrosidase (GCase) in human, will lead to GD whose symptoms include deficits in liver function, skeletal disorders, and in some cases severe neurological complications. Recent human genome sequencing studies have demonstrated that genetic variations in GBA1 constitute the largest known risk factor for Parkinson’s disease. To better understand the functional consequence of glucocerebrosidas

Background: Parkinson's disease (PD) is characterized by the formation of proteinaceous aggregates of α-synuclein (α-syn) in cell bodies and neurites of Substantia Nigra pars compacta (SNpc) dopaminergic neurons, eventually causing cell death. Interestingly, defective activity or mutations in GBA1, the gene encoding the lysosomal enzyme Glucocerebrosidase (GCase), are the strongest risk factor to develop PD. Based on this evidence, reverting the cytological and molecular abnormalities caused by GCase mutations or enhancing the activity of the wild type enzyme may represent a feasible therapeut

The aim of this study was to investigate the ability of GT-02287 to rescue nest-building behaviour following delayed administration in a mouse model of GBA1-Parkinson's disease (GBA1-PD). Nest building is a non-invasive test to study activities of daily living and cognitive performance in rodent models. GT-02287 is an orally bioavailable, brain penetrant, small-molecule structurally targeted allosteric regulator that binds to glucocerebrosidase (GCase), stabilizes it, and increases its function by chaperoning it to the lysosome. It is currently in Phase 1 clinical development for the treatmen