Mechanisms of Glucocerebrosidase Dysfunction in Parkinson’s Disease

2023/02/22 by Diptaman Chatterjee, Dimitri Krainc · 16 citations
Biochemistry, Genetics and Molecular Biology · Medicine · Neuroscience · #Bioinformatics #Biology #Cellular transport and secretion #Dementia #Disease #Glucocerebrosidase #Internal medicine #Lewy body #Lysosomal Storage Disorders Research #Medicine #Neurodegeneration #Neuroscience #Parkinson's Disease Mechanisms and Treatments #Parkinson's disease

paper · doi:10.1016/j.jmb.2023.168023

openalex publication_date 2023/02/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Beta-glucocerebrosidase is a lysosomal hydrolase, encoded by GBA1 that represents the most common risk gene associated with Parkinson's disease (PD) and Lewy Body Dementia. Glucocerebrosidase dysfunction has been also observed in the absence of GBA1 mutations across different genetic and sporadic forms of PD and related disorders, suggesting a broader role of glucocerebrosidase in neurodegeneration. In this review, we highlight recent advances in mechanistic characterization of glucocerebrosidase function as the foundation for development of novel therapeutics targeting glucocerebrosidase in PD and related disorders.

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• Detection of ER Stress in iPSC-Derived Neurons Carrying the p.N370S Mutation in the GBA1 Gene. [europepmc]
• Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease. [europepmc]
• The GBA1 K198E Variant Is Associated with Suppression of Glucocerebrosidase Activity, Autophagy Impairment, Oxidative Stress, Mitochondrial Damage, and Apoptosis in Skin Fibroblasts. [europepmc]
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• Protective Effect of the LRRK2 Kinase Inhibition in Human Fibroblasts Bearing the Genetic Variant GBA1 K198E: Implications for Parkinson's Disease. [europepmc]
• Using network toxicology and molecular docking to identify core targets and pathways underlying tacrolimus-induced tremor in organ transplant recipients. [europepmc]
• p.N370S GBA1 Mutation Influences the Morphology and Lipid Composition of Extracellular Vesicles in Blood Plasma from Patients with Parkinson's Disease. [europepmc]
• MAPL regulates gasdermin-mediated release of mtDNA from lysosomes to drive pyroptotic cell death. [europepmc]
• Exploring the relationship between GBA1 host genotype and gut microbiome in the GBA1 L444P/WT mouse model: implications for Parkinson's disease pathogenesis. [europepmc]
• Secondary Mitochondrial Dysfunction in Gaucher Disease Type I, II and III-Review of the Experimental and Clinical Evidence. [europepmc]
• Effects of glucocerebrosidase gene variations on the risk of Parkinson's disease dementia: a meta-analysis. [europepmc]
• Underlying Mechanisms of GBA1 in Parkinson's Disease and Dementia with Lewy Bodies: Narrative Review. [europepmc]
• Lysosomal homeostasis at the crossroads of neurodegeneration [europepmc]

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