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Catalog
ASAP is committed to accelerating the pace of discovery and informing a path to a cure for Parkinson’s disease through collaboration, research-enabling resources, and data sharing. We’ve created this catalog to showcase the research outputs and tools developed by ASAP-funded programs.
Protocol
Collection of protocols for paper: “Glucocerebrosidase, a Parkinson´s disease-associated protein, is imported into mitochondria and regulates complex I assembly and function”
This is a collection of protocols used in a recent pre-print by the Deleidi Lab, Team Schapira. You can access pre-print at https://doi.org/10.21203/rs.3.rs-1521848/v1
Teams
Lab Resource
x4 GBA plasmids
The below plasmids are deposited and available via Addgene: https://www.addgene.org/Anthony_Schapira/. These have been used in publication: 10.1093/hmg/ddac233
188580 WT GBA pcDNA3.1 GBA (Homo sapiens)
188581 E326K GBA pcDNA3.1 GBA (Homo sapiens)
188582 L444P GBA pcDNA3.1 GBA (Homo sapiens)
188583 N370S GBA pcDNA3.1 GBA (Homo sapiens)
Teams
Article
Genetic variations in GBA1 and LRRK2 genes: Biochemical and clinical consequences in Parkinson disease
Review: This review compares GBA1 and LRRK2-associated PD, and highlights possible genotype-phenotype associations for GBA1 and LRRK2 separately, based on biochemical consequences of single variants.
Teams
Code
Single cell analysis of iPSC-derived midbrain organoids
The following script was used for analysis of gene corrected (GC) versus GBA1 mutant (MUT) midbrain organoids. The purpose was to combine, filter, integrate, and identify clusters and differentially expressed genes sets.
Teams
Article
GBA Variants and Parkinson Disease: Mechanisms and Treatments
Review: The GBA gene encodes for the lysosomal enzyme glucocerebrosidase (GCase). Around 5–15% of PD patients have mutations in the GBA gene. This review discusses the pathways associated with GBA-PD and highlights potential treatments which may act to target GCase and prevent neurodegeneration.
Teams
Article
Sex-specific microglial responses to glucocerebrosidase inhibition: relevance to GBA1-linked Parkinson’s disease
Preprint: To elucidate the impact of sex-specific microglia heterogenicity to the susceptibility of neuronal stress, the authors analyzed the dynamic changes in shape and motility occurring in primary mouse microglia following pro-inflammatory or neurotoxic insults, thus finding sex-specific responses of microglial subpopulations.
Teams
Protocol
Midbrain-like Organoids generation from hiPSCs
Protocol for generating midbrain organoids from human iPSCs. In this protocol we describe the differentiation of human induced pluripotent stem cells (hiPSCs) into human midbrain-like organoids (hMLOs). This protocol has been developed based from several published protocols.
Teams
Article
The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines
Preprint: Although the E326K variant is one of the most common GBA variants associated with PD, there is limited understanding of its biochemical effects. Here, the authors characterize homozygous and heterozygous E326K variants in human fibroblasts.
Teams
Article
Bile acids and neurological disease
Review: This review focuses on how bile acids are being used in clinical trials to treat neurological diseases due to their central involvement with the gut-liver-brain axis and their physiological and pathophysiological roles in both normal brain function and multiple neurological diseases.
Teams
Article
LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson’s disease
Published: Recent work suggests that LRRK2 kinase activity can modulate glucocerebrosidase (GCase) function. The authors investigated the relationship between LRRK2 and GBA1 by assessing GCase activity and found a positive correlation between the activities of LRRK2 and GCase in different cellular and ex vivo models. View original preprint.
Teams
Article
Neuronal hyperactivity–induced oxidant stress promotes in vivo α-synuclein brain spreading
Published: This study investigated the relationship between neuronal activity and interneuronal transfer of α-synuclein, a Parkinson-associated protein, and elucidated mechanisms underlying this relationship.
Teams
Teams
Article
Sphingolipid changes in Parkinson L444P GBA mutation fibroblasts promote α-synuclein aggregation
Publication: In this study, the lipid membrane composition of fibroblasts isolated from control subjects, patients with idiopathic Parkinson’s disease and Parkinson’s disease patients carrying the L444P GBA mutation (PD-GBA) was assayed using shotgun lipidomics. Findings suggest that L44P GBA mutations have a distinctly altered membrane lipid profile. View original preprint.
Teams
Dataset
The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines
The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines. Associated with publication 10.1101/2022.06.01.494130.
Teams