ArticleFrontiers in cellular neuroscience2022
WHOPPA Enables Parallel Assessment of Leucine-Rich Repeat Kinase 2 and Glucocerebrosidase Enzymatic Activity in Parkinson's Disease Monocytes.
Article in Frontiers in cellular neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- LRRK2-targeting antisense oligonucleotide in Parkinson's disease: a phase 1 randomized controlled trial.Nature medicine · 2026Trial
- Profiling peripheral immune cells in Parkinson's disease: A scoping review.Journal of Parkinson's disease · 2026Review
- Ex Vivo LRRK2 Activation in Asian G2385R and R1628P Variant Carriers and Idiopathic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- LRRK2 kinase mediates increased GCase activity in microglia in response to IFNγ-induced proinflammatory stimulation.NPJ Parkinson's disease · 2026Article
- Parkinson's-Linked LRRK2 and GBA1 Mutations Modulate the Peripheral Immune Response to Pseudomonas aeruginosa.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Repurposing glucagon-like peptide-1 receptor agonists for the treatment of neurodegenerative disorders.Nature aging · 2026Review
- Interferon gamma stimulates coordinated changes in LRRK2, GCase, and cathepsin activities in idiopathic and genetic Parkinson's disease monocytes.NPJ Parkinson's disease · 2025Article
- Review
- Inflammation and IL-4 regulate Parkinson's and Crohn's disease associated kinase LRRK2.EMBO reports · 2025Article
- Leucine-rich repeat kinase 2 biomarkers for Parkinson's disease.The Biochemical journal · 2025Review
- Peripheral immune cell response to stimulation stratifies Parkinson's disease progression from prodromal to clinical stages.Communications biology · 2025Article
- TheScience translational medicine · 2024Article
- Peripheral Blood Immune Cells from Individuals with Parkinson's Disease or Inflammatory Bowel Disease Share Deficits in Iron Storage and Transport that are Modulated by Non-Steroidal Anti-Inflammatory Drugs.bioRxiv : the preprint server for biology · 2024Article
- A potential patient stratification biomarker for Parkinson´s disease based on LRRK2 kinase-mediated centrosomal alterations in peripheral blood-derived cells.NPJ Parkinson's disease · 2024Article
- ASO-mediated knockdown or kinase inhibition ofMolecular therapy. Nucleic acids · 2023Article
- Perspective on the current state of the LRRK2 field.NPJ Parkinson's disease · 2023Review
- Mechanisms of Glucocerebrosidase Dysfunction in Parkinson's Disease.Journal of molecular biology · 2023Review
- Glucocerebrosidase activity and lipid levels are related to protein pathologies in Parkinson's disease.NPJ Parkinson's disease · 2023Article
- The interplay between monocytes, α-synuclein and LRRK2 in Parkinson's disease.Biochemical Society transactions · 2023Review
- Live cellFrontiers in cellular neuroscience · 2023Article
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Both leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GCase) are promising targets for the treatment of Parkinson's disease (PD). Evidence suggests that both proteins are involved in biological pathways involving the lysosome. However, studies to date have largely investigated the enzymes in isolation and any relationship between LRRK2 and GCase remains unclear. Both enzymes are highly expressed in peripheral blood monocytes and have been implicated in immune function and inflammation. To facilitate the standardized measurement of these readouts in large cohorts of samples collected from persons with PD across the globe, we developed and optimized a sample collection and processing protocol with parallel flow cytometry assays. Assay parameters were first optimized using healthy control peripheral blood mononuclear cells (PBMCs), and then LRRK2 and GCase activities were measured in immune cells from persons with idiopathic PD (iPD). We tested the ability of this protocol to deliver similar results across institutes across the globe, and named this protocol the Wallings-Hughes Optimized Protocol for PBMC Assessment (WHOPPA). In the application of this protocol, we found increased LRRK2 levels and stimulation-dependent enzymatic activity, and decreased GBA index in classical iPD monocytes, as well as increased cytokine release in PD PBMCs. WHOPPA also demonstrated a strong positive correlation between LRRK2 levels, pRab10 and HLA-DR in classical monocytes from subjects with iPD. These data support a role for the global use of WHOPPA and expression levels of these two PD-associated proteins in immune responses, and provide a robust assay to determine if LRRK2 and GCase activities in monocytes have potential utility as reliable and reproducible biomarkers of disease in larger cohorts of subjects with PD.
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