Bidirectional regulation of glycoprotein nonmetastatic melanoma protein B by β-glucocerebrosidase deficiency in isogenic dopaminergic neurons from a patient with Gaucher disease and parkinsonism.

Variants in are common genetic risk factors for several synucleinopathies. The increased risk has been attributed to the toxic effects of misfolded glucocerebrosidase (GCase) (gain-of-function), and the accumulation of lipid substrates due to reduced enzyme activity (loss-of-function). To delineate pathogenicity, an iPSC line was generated from a patient with both type 1 Gaucher disease (: N370S/N370S; p.

Evaluation of Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons from Siblings with Gaucher Disease Discordant for Parkinsonism.

Background: In Gaucher disease (GD), glucocerebrosidase (GCase) deficiency results from biallelic pathogenic GBA1 variants. While GBA1 variants are a major risk factor for Parkinson's disease (PD), most patients with GD never develop parkinsonism.

Objectives: To understand factors impacting PD penetrance in patients with GD by comparing induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DANs) from GD siblings discordant for PD.

Proteomic Analysis of Endemic Viral Infections in Neurons offers Insights into Neurodegenerative Diseases.

Endemic viral infections with low pathogenicity are often overlooked due to their mild symptoms, yet they can exert long-term effects on cellular function and contribute to disease pathogenesis. While viral infections have been implicated in neurodegenerative disorders, their impact on the neuronal proteome remains poorly understood. Here, we differentiated human induced pluripotent stem cells (KOLF2.

Comparative study of enriched dopaminergic neurons from siblings with Gaucher disease discordant for parkinsonism.

Inducible pluripotent stem cells (iPSCs) derived from patient samples have significantly enhanced our ability to model neurological diseases. Comparative studies of dopaminergic (DA) neurons differentiated from iPSCs derived from siblings with Gaucher disease discordant for parkinsonism provides a valuable avenue to explore genetic modifiers contributing to -associated parkinsonism in disease-relevant cells. However, such studies are often complicated by the inherent heterogeneity in differentiation efficiency among iPSC lines derived from different individuals.